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David W Hoskin - One of the best experts on this subject based on the ideXlab platform.
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10 Gingerol inhibits ovarian cancer cell growth by inducing g2 arrest
Advanced Pharmaceutical Bulletin, 2019Co-Authors: Andrea Rasmussen, Kaylee Murphy, David W HoskinAbstract:Purpose: Gingerol homologs found in the rhizomes of ginger plants have the potential to benefit human health, including the prevention and treatment of cancer. This study evaluated the effect of 10-Gingerol on ovarian cancer cell (HEY, OVCAR3, and SKOV-3) growth. Methods: Cell growth was measured by MTT assays, flow cytometry was used to assess cell proliferation, cytotoxicity and cell cycle progression, and western blotting was used to measure cyclin protein expression. Results: Ovarian cancer cells that were treated with 10-Gingerol experienced a time- and dose-dependent decrease in cell number, which was due to a reduction in cell proliferation rather than a cytotoxic effect. Reduced proliferation of 10-Gingerol-treated ovarian cancer cells was associated with an increased percentage of cells in G2 phase of the cell cycle and a corresponding reduction in the percentage of cells in G1. Ovarian cancer cells also showed decreased cyclin A, B1, and D3 expression following exposure to 10-Gingerol. Conclusion: These findings revealed that 10-Gingerol caused a G2 arrest-associated suppression of ovarian cancer cell growth, which may be exploited in the management of ovarian cancer.
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10 Gingerol a major phenolic constituent of ginger root induces cell cycle arrest and apoptosis in triple negative breast cancer cells
Experimental and Molecular Pathology, 2017Co-Authors: Megan M Bernard, Jason R Mcconnery, David W HoskinAbstract:The ginger rhizome is rich in bioactive compounds, including [6]-Gingerol, [8]-Gingerol, and [10]-Gingerol; however, to date, most research on the anti-cancer activities of Gingerols have focused on [6]-Gingerol. In this study, we compared [10]-Gingerol with [8]-Gingerol and [6]-Gingerol in terms of their ability to inhibit the growth of human and mouse mammary carcinoma cells. A colorimetric assay based on the enzymatic reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide revealed that [10]-Gingerol was more potent than [6]-Gingerol and at least as potent as [8]-Gingerol for the inhibition of triple-negative human (MDA-MB-231, MDA-MB-468) and mouse (4T1, E0771) mammary carcinoma cell growth. Further investigation of [10]-Gingerol showed that it suppressed the growth of estrogen receptor-bearing (MCF-7, T47D) and HER2-overexpressing (SKBR3) breast cancer cells. The inhibitory effect of [10]-Gingerol on the growth of MDA-MB-231 cells was associated with a reduction in the number of rounds of cell division and evidence of S phase-cell cycle arrest, as well as induction of apoptosis due to mitochondrial outer membrane permeabilization and the release of proapoptotic mitochondrial cytochrome c and SMAC/DIABLO into the cytoplasm. Surprisingly, killing of MDA-MB-231 cells by [10]-Gingerol was not affected by a pan-caspase inhibitor (zVAD-fmk) or an anti-oxidant (N-acetylcysteine), suggesting that the cytotoxic effect of [10]-Gingerol did not require caspase activation or the accumulation of reactive oxygen species. These findings suggest that further investigation of [10]-Gingerol is warranted for its possible use in the treatment of breast cancer.
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differential inhibition of t lymphocyte proliferation and cytokine synthesis by 6 Gingerol 8 Gingerol and 10 Gingerol
Phytotherapy Research, 2015Co-Authors: Megan M Bernard, Suzanne J Furlong, Melanie Power R Coombs, David W HoskinAbstract:[6]-Gingerol, [8]-Gingerol, and [10]-Gingerol are pungent components of fresh ginger, extracts of which inhibit various components of the inflammatory response. Because little is known regarding the effect of Gingerols with different unbranched alkyl side chain lengths on the activation and effector function of T lymphocytes, we compared the effects of [6]-Gingerol, [8]-Gingerol, and [10]-Gingerol on murine T lymphocyte proliferation, expression of CD25 and CD69 activation markers, cytokine synthesis, and interleukin (IL)-2 receptor signaling. All three Gingerols inhibited DNA synthesis by T lymphocytes, as well as interferon-γ synthesis. In contrast, only [8]-Gingerol and [10]-Gingerol inhibited CD25 and CD69 expression, and IL-2 synthesis. None of the Gingerols affected IL-4 synthesis. Exogenous IL-2 enhanced T lymphocyte proliferation in the presence of [6]-Gingerol but did not significantly increase T lymphocyte proliferation in the presence of [8]-Gingerol or [10]-Gingerol. In line with this finding, [8]-Gingerol and [10]-Gingerol impaired IL-2-induced proliferation of CTLL-2 cells, but constitutive CD25 expression was unaffected, indicating inhibition of IL-2 receptor signaling. In general, [10]-Gingerol and [8]-Gingerol were more potent inhibitors of T lymphocytes than [6]-Gingerol. Suppression of T lymphocyte responses by Gingerols suggests that these phytochemicals may be beneficial in chronic inflammatory conditions associated with excessive or inappropriate T lymphocyte activation. Copyright © 2015 John Wiley & Sons, Ltd.
Jiguo Zhang - One of the best experts on this subject based on the ideXlab platform.
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therapeutic effects of 6 Gingerol 8 Gingerol and 10 Gingerol on dextran sulfate sodium induced acute ulcerative colitis in rats
Phytotherapy Research, 2017Co-Authors: Feng Zhang, Jiguo ZhangAbstract:Ulcerative colitis is one of the most common types of inflammatory bowel disease and is multifactorial and relapsing. 6-Gingerol, a component of Gingerols extracted from ginger (Zingiber officinale), has been reported to improve ulcerative colitis. The present study aims to investigate the therapeutic efficacy of two analogous forms of 6-Gingerol, 8-Gingerol, and 10-Gingerol, on ulcerative colitis. Colitis was induced in rats through consumption of 5% (w/v) dextran sulfate sodium drinking water for 7 consecutive days. 6-Gingerol, 8-Gingerol, and 10-Gingerol were then given intraperitoneally at doses of 30 mg kg−1 d−1 for another 7 days, respectively. Body weight change, disease activity index, inflammatory cytokines, and oxidative stress indices were measured, and the colonic tissue injuries were assessed macroscopically and histopathologically. Results showed that all three Gingerols attenuated colitic symptoms evoked by dextran sulfate sodium, significantly elevated superoxide dismutase activity, decreased malondialdehyde levels and myeloperoxidase activity in the colon tissue, and markedly reduced the content of tumor necrosis factor alpha and Interleukin 1 beta in the serum. Histological observations showed that all three Gingerols obviously accelerated mucosal damage healing. It is concluded that 6-Gingerol, 8-Gingerol, and 10-Gingerol, the three analogues, have a strong and relatively equal efficacy in the treatment of colitis. Copyright © 2017 John Wiley & Sons, Ltd.
Angelina Maria Fuzer - One of the best experts on this subject based on the ideXlab platform.
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[10]-Gingerol Affects Multiple Metastatic Processes and Induces Apoptosis in MDAMB- 231 Breast Tumor Cells.
Anti-cancer Agents in Medicinal Chemistry, 2019Co-Authors: Angelina Maria Fuzer, Ana Carolina Baptista Moreno Martin, Amanda Blanque Becceneri, Paulo C Vieira, James Almada Da Silva, Marcia R CominettiAbstract:Triple Negative Breast Cancer (TNBC) represents the approximately 15% of breast cancers that lack expression of Estrogen (ER) and Progesterone Receptors (PR) and do not exhibit amplification of the human epidermal growth factor receptor 2 (HER2) gene, imposing difficulties to treatment. Interactions between tumor cells and their microenvironment facilitate tumor cell invasion in the surrounding tissues, intravasation through newly formed vessels, and dissemination to form metastasis. To treat metastasis from breast and many other cancer types, chemotherapy is one of the most extensively used methods. However, its efficacy and safety remain a primary concern, as well as its toxicity and other side effects. Thus, there is increasing interest in natural antitumor agents. In a previous work, we have demonstrated that [10]-Gingerol is able to revert malignant phenotype in breast cancer cells in 3D culture and, moreover, to inhibit the dissemination of TNBC to multiple organs including lung, bone and brain, in spontaneous and experimental in vivo metastasis assays in mouse model. This work aims to investigate the in vitro effects of [10]-Gingerol, using human MDA-MB-231TNBC cells, in comparison to non-tumor MCF-10A breast cells, in order to understand the antitumor and antimetastatic effects found in vivo and in a 3D environment. We investigated different steps of the metastatic process in vitro, such as cell migration, invasion, adhesion and MMP activity. In addition, we analyzed the anti-apoptotic and genotoxic effects of [10]-Gingerol using PEAnnexin, DNA fragmentation, TUNEL and comet assays, respectively. [10]-Gingerol was able to inhibit cell adhesion, migration, invasion and to induce apoptosis more effectively in TNBC cells, when compared to non-tumor cells, demonstrating that these mechanisms can be involved in the antitumor and antimetastatic effects of [10]-Gingerol, found both in 3D culture and in vivo. Taken together, results found here are complementary to previous studies of our group and others and demonstrate that additional mechanisms, besides apoptotic cell death, is used by [10]-Gingerol to accomplish its antitumor and antimetastatic effects. Our results indicate a potential for this natural compound as an antitumor molecule or as an adjuvant for chemotherapeutics already used in the clinic. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
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abstract a53 10 Gingerol interferes with the adhesion of mda mb 231 tumor cells to extracellular matrix
Molecular Cancer Research, 2018Co-Authors: Angelina Maria Fuzer, Ana Carolina Baptista Moreno Martin, Rebeka Tomasin, Amanda Blanque Becceneri, Paulo C Vieira, James Almada Da Silva, Carolina Venturini Uliana, Rafael Luis Bressani Lino, Heloisa Sobreiro Selistre De Araujo, Rodolpho De Campos BragaAbstract:Breast cancer is one of the most common malignant diseases in women worldwide. In developing countries, it is the second highest cause of death in women. Triple-negative breast cancer (TNBC) represents the approximately 15% of breast cancers that lack expression of estrogen (ER) and progesterone receptors (PR) and do not exhibit amplification of the human epidermal growth factor receptor 2 (HER2) gene. Metastatic process is described as a cascade of events. Normal cells are transformed into tumor cells due to mutations in genes that regulate critical pathways, producing an imbalance between proliferation and cell death that eventually leads to the formation of a primary tumor. Further interactions with the stromal microenvironment surrounding tumor cells and extracellular matrix (ECM) proteins contribute to the formation of new vessels. These interactions facilitate tumor cell invasion of surrounding tissues, intravasation through newly formed vessels, and dissemination to other tissues, to form secondary tumors. To treat metastasis from breast and many other cancer types, chemotherapy is one of the most extensively used methods. However, its efficacy and safety remain a primary concern, as well as its toxicity and other side effects. Thus, there is increasing interest in naturally occurring cancer antitumor agents. Ginger (Zingiber officinale Roscoe) is widely used worldwide as a food, spice, and herb. Recently we have demonstrated that [10]-Gingerol is able to revert malignant phenotype in breast cancer cells in 3D culture and, moreover, to inhibit the dissemination of TNBC to multiple organs including to lung, bone, and brain, in spontaneous and experimental in vivo metastasis assays. The aim of this work was to investigate the effects of [10]-Gingerol on the adhesion properties of MDA-MB-231 cells to the extracellular matrix (ECM). We hypothesized that, at least in part, these effects are mediated through [10]-Gingerol interactions with αVβ3 integrin. Human MDA-MB-231 breast tumor cells were obtained from ATCC and maintained at 37°C, 5% CO2 in Dulbecco’s Modified Eagle Medium, containing FBS 10%). Ninety-six well plates were coated vitronectin (1µg/well) dissolved in adhesion buffer at 4oC overnight, blocked for 2h with 1% BSA, and the wells washed with 100μL of adhesion buffer. MDA-MB-231 cells (5x105/mL) were pretreated for 30min with [10]-Gingerol (1-100μM) in a humidified incubator with 5% CO2 at 37°C and 100µL of cell suspension plated into wells and incubated as above for a further 1 hour. Nonadherent cells were gently removed by washing and adherent cells were fixed with 100µl of 4% paraformaldehyde solution for 20min, stopped with PBS-Glycine, stained with DAPI, and counted in a HCS microscope. Data from docking were analyzed in AutoDock plugin for PyMOL and the two-dimensional scheme of interaction was obtained by LiPlot+.The electrochemical study of the interaction between [10]-Gingerol and αVβ3 integrin was performed using disposable electrochemical cells (DCell), which are composed by a carbon working electrode, an Ag|AgCl pseudo-reference electrode, and a carbon counter electrode. Measurements were carried out employing the potentiostat DropSens 8000 and Dropview software 8400. The interaction of [10]-Gingerol and αVβ3 integrin was evaluated by the changes in the [10]-Gingerol electrochemical responses. For this, different amounts of standard αVβ3 integrin solution in PBS pH 7.0 were added and mixed homogeneously with a solution composed of 10µM [10]-Gingerol. The differences of peak current were used to demonstrate the changes of electrochemical responses. We found that [10]-Gingerol was able to inhibit TNBC cell adhesion to vitronectin ECM with more specificity compared to the other ECM components investigated, demonstrating that this compound interferes in this step of the metastatic process. We proposed that these effects could be, at least in part, resulting from the interaction between [10]-Gingerol and αVβ3 integrin, as demonstrated by electrochemical and docking studies. Citation Format: Angelina Maria Fuzer, Ana Carolina B. M. Martin, Rebeka Tomasin, Carolina Venturini Uliana, Amanda Blanque Becceneri, Rafael L. Bressani Lino, James Almada da Silva, Paulo Cezar Vieira, Heloisa Sobreiro Selistre de Araujo, Rodolpho de Campos Braga, Ronaldo Censi Faria, Marcia Regina Cominetti. [10]-Gingerol interferes with the adhesion of MDA-MB-231 tumor cells to extracellular matrix [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr A53.
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10 Gingerol reverts malignant phenotype of breast cancer cells in 3d culture
Journal of Cellular Biochemistry, 2017Co-Authors: Angelina Maria Fuzer, Joni D Mott, Marcia R CominettiAbstract:Author(s): Fuzer, Angelina M; Lee, Sun-Young; Mott, Joni D; Cominetti, Marcia R | Abstract: Breast cancer is a complex and multifactorial disease. Tumors have a heterogeneous microenvironment, which have multiple interactions with other cell types, greatly influencing the behavior of tumor cells and response to therapy. The 3D culture mimics the microenvironment better found in vivo and is more appropriated than the traditional 2D culture made from plastic to test the cellular response to drugs. To investigate the effects of [10]-Gingerol on breast tumor cells, we used physiologically relevant three-dimensional (3D) cultures of malignant and non-malignant human breast cells grown in laminin-rich extracellular matrix gels (lr-ECM). Our results showed selective cytotoxicity of [10]-Gingerol against the malignant T4-2 breast cancer cell line compared to non-malignant S1 cells. The compound reverted the malignant phenotype of the cancer cells, downregulating the expression of epidermal growth factor receptor (EGFR) and β1-integrin. Moreover, [10]-Gingerol induced apoptosis in this cell line. These results suggest that [10]-Gingerol may be an effective compound to use as adjuvant therapy in breast cancer treatment. J. Cell. Biochem. 118: 2693-2699, 2017. © 2017 Wiley Periodicals, Inc.
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10 Gingerol induces apoptosis and inhibits metastatic dissemination of triple negative breast cancer in vivo
Oncotarget, 2017Co-Authors: Ana Carolina Baptista Moreno Martin, Angelina Maria Fuzer, Rebeka Tomasin, Amanda Blanque Becceneri, James Almada Da Silva, Delphine Denoyer, Katherine A Mcintyre, Helen B Pearson, Aadya Nagpal, Xiawei LingAbstract:// Ana Carolina B.M. Martin 1, * , Angelina M. Fuzer 1, * , Amanda B. Becceneri 1 , James Almada da Silva 2 , Rebeka Tomasin 1 , Delphine Denoyer 3 , Soo-Hyun Kim 4 , Katherine A. McIntyre 5 , Helen B. Pearson 6 , Belinda Yeo 7 , Aadya Nagpal 7 , Xiawei Ling 4 , Heloisa S. Selistre-de-Araujo 8 , Paulo Cezar Vieira 2 , Marcia R. Cominetti 1, * and Normand Pouliot 4, 5, 7, * 1 Department of Gerontology, Federal University of Sao Carlos, Sao Carlos, SP, Brazil 2 Department of Chemistry, Federal University of Sao Carlos, Sao Carlos, SP, Brazil 3 Metals in Medicine Laboratory, Centre for Cellular and Molecular Biology (CCMB), Melbourne Burwood Campus, Deakin University, VIC, Australia 4 Department of Pathology and University of Melbourne, VIC, Australia 5 Sir Peter MacCallum Department of Oncology, University of Melbourne, VIC, Australia 6 European Cancer Stem Cell Research Institute, Cardiff University, Cathays, Cardiff, UK 7 Matrix Microenvironment and Metastasis Laboratory, Olivia Newton-John Cancer Research Institute, School of Cancer Medicine, La Trobe University, Heidelberg, Australia 8 Department of Physiological Sciences, Federal University of Sao Carlos, Sao Carlos, SP, Brazil * Authors contributed equally to this work and share co-senior authorship Correspondence to: Marcia R. Cominetti, email: mcominetti@ufscar.br Keywords: Gingerol, breast cancer, cell cycle, apoptosis, animal models Received: January 23, 2017 Accepted: July 29, 2017 Published: August 10, 2017 ABSTRACT There is increasing interest in the use of non-toxic natural products for the treatment of various pathologies, including cancer. In particular, biologically active constituents of the ginger oleoresin ( Zingiber officinale Roscoe) have been shown to mediate anti-tumour activity and to contribute to the anti-inflammatory, antioxidant, antimicrobial, and antiemetic properties of ginger. Here we report on the inhibitory properties of [10]-Gingerol against metastatic triple negative breast cancer (TNBC) in vitro and in vivo . We show that [10]-Gingerol concentration-dependently induces apoptotic death in mouse and human TNBC cell lines in vitro . In addition, [10]-Gingerol is well tolerated in vivo , induces a marked increase in caspase-3 activation and inhibits orthotopic tumour growth in a syngeneic mouse model of spontaneous breast cancer metastasis. Importantly, using both spontaneous and experimental metastasis assays, we show for the first time that [10]-Gingerol significantly inhibits metastasis to multiple organs including lung, bone and brain. Remarkably, inhibition of brain metastasis was observed even when treatment was initiated after surgical removal of the primary tumour. Taken together, these results indicate that [10]-Gingerol may be a safe and useful complementary therapy for the treatment of metastatic breast cancer and warrant further investigation of its efficacy, either alone or in combination with standard systemic therapies, in pre-clinical models of metastatic breast cancer and in patients.
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abstract b40 10 Gingerol as a pro apoptotic molecule in triple negative breast cancer
Molecular Cancer Research, 2017Co-Authors: Ana Carolina Baptista Moreno Martin, Angelina Maria Fuzer, Rebeka Tomasin, Amanda Blanque Becceneri, Paulo C Vieira, Marcia R CominettiAbstract:The aim of this work was to study the pro-apoptotic effects of [10]-Gingerol and connect them to anti-tumor and anti-metastatic activities in triple negative breast cancer (TNBC) cell lines and in an spontaneous triple negative breast cancer model in vivo. Breast cancer has the highest incidence among women and metastasis is the major cause of death in cancer. TNBC affects 20% of women with breast cancer. This cancer type is very aggressive and has a high propensity to form lung and brain metastases. Nowadays, there is no effective treatment for TNBC and therefore, new therapies are required. Studies to discovery new molecules to be used in more efficient treatments for this disease are essential. Molecules that can interfere with cell proliferation, migration, invasion, apoptosis and cell cycle can be used as a model or tools to develop new anti-metastatic drugs. Epidemiologic studies have shown that Asian populations have lower incidence of breast cancer comparing to western populations. This has been attributed in part to differences in dietary habits. In particular, Gingerols, natural compounds extracted from ginger rhizomes, have been shown to present anti-cancer properties against various tumor cell types in vitro and in vivo. MTT assay was performed to verify the inhibitory effects of [10]-Gingerol on cell proliferation. To investigate [10]-Gingerol mechanisms of action, apoptosis, cell cycle assays and TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) were performed. For the in vivo data an spontaneous model of breast cancer metastasis was used. Results : [10]-Gingerol was able to inhibit cell proliferation in different cell lines. In the murine cell line (4T1Br4), [10]-Gingerol induced apoptosis, cell cycle arrest at sub-G0 phase and also induced DNA damage demonstrated by TUNEL assay, therefore interfering with DNA and provoking its damage. [10]-Gingerol inhibited lung, bone and brain metastases in an intra-mammary fat pad spontaneous breast cancer model. Conclusion : [10]-Gingerol showed to be a non-toxic compound with anti-proliferative and DNA damaging effects, inducing cell apoptosis in vitro and also inhibiting lung, bone and brain metastases in a spontaneous TNBC model in vivo. Patent deposit: BR 10 2015 024093 7. Approved by ethical committee – E507 and 3224-1. Citation Format: Ana Carolina B. M. Martin, Rebeka Tomasin, Amanda Blanque Becceneri, Angelina Fuzer, Paulo Cezar Vieira, Marcia Regina Cominetti. [10]-Gingerol as a pro-apoptotic molecule in triple negative breast cancer [abstract]. In: Proceedings of the AACR Special Conference on DNA Repair: Tumor Development and Therapeutic Response; 2016 Nov 2-5; Montreal, QC, Canada. Philadelphia (PA): AACR; Mol Cancer Res 2017;15(4_Suppl):Abstract nr B40.
Feng Zhang - One of the best experts on this subject based on the ideXlab platform.
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therapeutic effects of 6 Gingerol 8 Gingerol and 10 Gingerol on dextran sulfate sodium induced acute ulcerative colitis in rats
Phytotherapy Research, 2017Co-Authors: Feng Zhang, Jiguo ZhangAbstract:Ulcerative colitis is one of the most common types of inflammatory bowel disease and is multifactorial and relapsing. 6-Gingerol, a component of Gingerols extracted from ginger (Zingiber officinale), has been reported to improve ulcerative colitis. The present study aims to investigate the therapeutic efficacy of two analogous forms of 6-Gingerol, 8-Gingerol, and 10-Gingerol, on ulcerative colitis. Colitis was induced in rats through consumption of 5% (w/v) dextran sulfate sodium drinking water for 7 consecutive days. 6-Gingerol, 8-Gingerol, and 10-Gingerol were then given intraperitoneally at doses of 30 mg kg−1 d−1 for another 7 days, respectively. Body weight change, disease activity index, inflammatory cytokines, and oxidative stress indices were measured, and the colonic tissue injuries were assessed macroscopically and histopathologically. Results showed that all three Gingerols attenuated colitic symptoms evoked by dextran sulfate sodium, significantly elevated superoxide dismutase activity, decreased malondialdehyde levels and myeloperoxidase activity in the colon tissue, and markedly reduced the content of tumor necrosis factor alpha and Interleukin 1 beta in the serum. Histological observations showed that all three Gingerols obviously accelerated mucosal damage healing. It is concluded that 6-Gingerol, 8-Gingerol, and 10-Gingerol, the three analogues, have a strong and relatively equal efficacy in the treatment of colitis. Copyright © 2017 John Wiley & Sons, Ltd.
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Therapeutic Effects of 6‐Gingerol, 8‐Gingerol, and 10‐Gingerol on Dextran Sulfate Sodium‐Induced Acute Ulcerative Colitis in Rats
Phytotherapy Research, 2017Co-Authors: Feng Zhang, Na Ma, Ji‐guo ZhangAbstract:Ulcerative colitis is one of the most common types of inflammatory bowel disease and is multifactorial and relapsing. 6-Gingerol, a component of Gingerols extracted from ginger (Zingiber officinale), has been reported to improve ulcerative colitis. The present study aims to investigate the therapeutic efficacy of two analogous forms of 6-Gingerol, 8-Gingerol, and 10-Gingerol, on ulcerative colitis. Colitis was induced in rats through consumption of 5% (w/v) dextran sulfate sodium drinking water for 7 consecutive days. 6-Gingerol, 8-Gingerol, and 10-Gingerol were then given intraperitoneally at doses of 30 mg kg−1 d−1 for another 7 days, respectively. Body weight change, disease activity index, inflammatory cytokines, and oxidative stress indices were measured, and the colonic tissue injuries were assessed macroscopically and histopathologically. Results showed that all three Gingerols attenuated colitic symptoms evoked by dextran sulfate sodium, significantly elevated superoxide dismutase activity, decreased malondialdehyde levels and myeloperoxidase activity in the colon tissue, and markedly reduced the content of tumor necrosis factor alpha and Interleukin 1 beta in the serum. Histological observations showed that all three Gingerols obviously accelerated mucosal damage healing. It is concluded that 6-Gingerol, 8-Gingerol, and 10-Gingerol, the three analogues, have a strong and relatively equal efficacy in the treatment of colitis. Copyright © 2017 John Wiley & Sons, Ltd.
Ana Carolina Baptista Moreno Martin - One of the best experts on this subject based on the ideXlab platform.
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[10]-Gingerol Affects Multiple Metastatic Processes and Induces Apoptosis in MDAMB- 231 Breast Tumor Cells.
Anti-cancer Agents in Medicinal Chemistry, 2019Co-Authors: Angelina Maria Fuzer, Ana Carolina Baptista Moreno Martin, Amanda Blanque Becceneri, Paulo C Vieira, James Almada Da Silva, Marcia R CominettiAbstract:Triple Negative Breast Cancer (TNBC) represents the approximately 15% of breast cancers that lack expression of Estrogen (ER) and Progesterone Receptors (PR) and do not exhibit amplification of the human epidermal growth factor receptor 2 (HER2) gene, imposing difficulties to treatment. Interactions between tumor cells and their microenvironment facilitate tumor cell invasion in the surrounding tissues, intravasation through newly formed vessels, and dissemination to form metastasis. To treat metastasis from breast and many other cancer types, chemotherapy is one of the most extensively used methods. However, its efficacy and safety remain a primary concern, as well as its toxicity and other side effects. Thus, there is increasing interest in natural antitumor agents. In a previous work, we have demonstrated that [10]-Gingerol is able to revert malignant phenotype in breast cancer cells in 3D culture and, moreover, to inhibit the dissemination of TNBC to multiple organs including lung, bone and brain, in spontaneous and experimental in vivo metastasis assays in mouse model. This work aims to investigate the in vitro effects of [10]-Gingerol, using human MDA-MB-231TNBC cells, in comparison to non-tumor MCF-10A breast cells, in order to understand the antitumor and antimetastatic effects found in vivo and in a 3D environment. We investigated different steps of the metastatic process in vitro, such as cell migration, invasion, adhesion and MMP activity. In addition, we analyzed the anti-apoptotic and genotoxic effects of [10]-Gingerol using PEAnnexin, DNA fragmentation, TUNEL and comet assays, respectively. [10]-Gingerol was able to inhibit cell adhesion, migration, invasion and to induce apoptosis more effectively in TNBC cells, when compared to non-tumor cells, demonstrating that these mechanisms can be involved in the antitumor and antimetastatic effects of [10]-Gingerol, found both in 3D culture and in vivo. Taken together, results found here are complementary to previous studies of our group and others and demonstrate that additional mechanisms, besides apoptotic cell death, is used by [10]-Gingerol to accomplish its antitumor and antimetastatic effects. Our results indicate a potential for this natural compound as an antitumor molecule or as an adjuvant for chemotherapeutics already used in the clinic. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
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abstract a53 10 Gingerol interferes with the adhesion of mda mb 231 tumor cells to extracellular matrix
Molecular Cancer Research, 2018Co-Authors: Angelina Maria Fuzer, Ana Carolina Baptista Moreno Martin, Rebeka Tomasin, Amanda Blanque Becceneri, Paulo C Vieira, James Almada Da Silva, Carolina Venturini Uliana, Rafael Luis Bressani Lino, Heloisa Sobreiro Selistre De Araujo, Rodolpho De Campos BragaAbstract:Breast cancer is one of the most common malignant diseases in women worldwide. In developing countries, it is the second highest cause of death in women. Triple-negative breast cancer (TNBC) represents the approximately 15% of breast cancers that lack expression of estrogen (ER) and progesterone receptors (PR) and do not exhibit amplification of the human epidermal growth factor receptor 2 (HER2) gene. Metastatic process is described as a cascade of events. Normal cells are transformed into tumor cells due to mutations in genes that regulate critical pathways, producing an imbalance between proliferation and cell death that eventually leads to the formation of a primary tumor. Further interactions with the stromal microenvironment surrounding tumor cells and extracellular matrix (ECM) proteins contribute to the formation of new vessels. These interactions facilitate tumor cell invasion of surrounding tissues, intravasation through newly formed vessels, and dissemination to other tissues, to form secondary tumors. To treat metastasis from breast and many other cancer types, chemotherapy is one of the most extensively used methods. However, its efficacy and safety remain a primary concern, as well as its toxicity and other side effects. Thus, there is increasing interest in naturally occurring cancer antitumor agents. Ginger (Zingiber officinale Roscoe) is widely used worldwide as a food, spice, and herb. Recently we have demonstrated that [10]-Gingerol is able to revert malignant phenotype in breast cancer cells in 3D culture and, moreover, to inhibit the dissemination of TNBC to multiple organs including to lung, bone, and brain, in spontaneous and experimental in vivo metastasis assays. The aim of this work was to investigate the effects of [10]-Gingerol on the adhesion properties of MDA-MB-231 cells to the extracellular matrix (ECM). We hypothesized that, at least in part, these effects are mediated through [10]-Gingerol interactions with αVβ3 integrin. Human MDA-MB-231 breast tumor cells were obtained from ATCC and maintained at 37°C, 5% CO2 in Dulbecco’s Modified Eagle Medium, containing FBS 10%). Ninety-six well plates were coated vitronectin (1µg/well) dissolved in adhesion buffer at 4oC overnight, blocked for 2h with 1% BSA, and the wells washed with 100μL of adhesion buffer. MDA-MB-231 cells (5x105/mL) were pretreated for 30min with [10]-Gingerol (1-100μM) in a humidified incubator with 5% CO2 at 37°C and 100µL of cell suspension plated into wells and incubated as above for a further 1 hour. Nonadherent cells were gently removed by washing and adherent cells were fixed with 100µl of 4% paraformaldehyde solution for 20min, stopped with PBS-Glycine, stained with DAPI, and counted in a HCS microscope. Data from docking were analyzed in AutoDock plugin for PyMOL and the two-dimensional scheme of interaction was obtained by LiPlot+.The electrochemical study of the interaction between [10]-Gingerol and αVβ3 integrin was performed using disposable electrochemical cells (DCell), which are composed by a carbon working electrode, an Ag|AgCl pseudo-reference electrode, and a carbon counter electrode. Measurements were carried out employing the potentiostat DropSens 8000 and Dropview software 8400. The interaction of [10]-Gingerol and αVβ3 integrin was evaluated by the changes in the [10]-Gingerol electrochemical responses. For this, different amounts of standard αVβ3 integrin solution in PBS pH 7.0 were added and mixed homogeneously with a solution composed of 10µM [10]-Gingerol. The differences of peak current were used to demonstrate the changes of electrochemical responses. We found that [10]-Gingerol was able to inhibit TNBC cell adhesion to vitronectin ECM with more specificity compared to the other ECM components investigated, demonstrating that this compound interferes in this step of the metastatic process. We proposed that these effects could be, at least in part, resulting from the interaction between [10]-Gingerol and αVβ3 integrin, as demonstrated by electrochemical and docking studies. Citation Format: Angelina Maria Fuzer, Ana Carolina B. M. Martin, Rebeka Tomasin, Carolina Venturini Uliana, Amanda Blanque Becceneri, Rafael L. Bressani Lino, James Almada da Silva, Paulo Cezar Vieira, Heloisa Sobreiro Selistre de Araujo, Rodolpho de Campos Braga, Ronaldo Censi Faria, Marcia Regina Cominetti. [10]-Gingerol interferes with the adhesion of MDA-MB-231 tumor cells to extracellular matrix [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr A53.
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10 Gingerol induces apoptosis and inhibits metastatic dissemination of triple negative breast cancer in vivo
Oncotarget, 2017Co-Authors: Ana Carolina Baptista Moreno Martin, Angelina Maria Fuzer, Rebeka Tomasin, Amanda Blanque Becceneri, James Almada Da Silva, Delphine Denoyer, Katherine A Mcintyre, Helen B Pearson, Aadya Nagpal, Xiawei LingAbstract:// Ana Carolina B.M. Martin 1, * , Angelina M. Fuzer 1, * , Amanda B. Becceneri 1 , James Almada da Silva 2 , Rebeka Tomasin 1 , Delphine Denoyer 3 , Soo-Hyun Kim 4 , Katherine A. McIntyre 5 , Helen B. Pearson 6 , Belinda Yeo 7 , Aadya Nagpal 7 , Xiawei Ling 4 , Heloisa S. Selistre-de-Araujo 8 , Paulo Cezar Vieira 2 , Marcia R. Cominetti 1, * and Normand Pouliot 4, 5, 7, * 1 Department of Gerontology, Federal University of Sao Carlos, Sao Carlos, SP, Brazil 2 Department of Chemistry, Federal University of Sao Carlos, Sao Carlos, SP, Brazil 3 Metals in Medicine Laboratory, Centre for Cellular and Molecular Biology (CCMB), Melbourne Burwood Campus, Deakin University, VIC, Australia 4 Department of Pathology and University of Melbourne, VIC, Australia 5 Sir Peter MacCallum Department of Oncology, University of Melbourne, VIC, Australia 6 European Cancer Stem Cell Research Institute, Cardiff University, Cathays, Cardiff, UK 7 Matrix Microenvironment and Metastasis Laboratory, Olivia Newton-John Cancer Research Institute, School of Cancer Medicine, La Trobe University, Heidelberg, Australia 8 Department of Physiological Sciences, Federal University of Sao Carlos, Sao Carlos, SP, Brazil * Authors contributed equally to this work and share co-senior authorship Correspondence to: Marcia R. Cominetti, email: mcominetti@ufscar.br Keywords: Gingerol, breast cancer, cell cycle, apoptosis, animal models Received: January 23, 2017 Accepted: July 29, 2017 Published: August 10, 2017 ABSTRACT There is increasing interest in the use of non-toxic natural products for the treatment of various pathologies, including cancer. In particular, biologically active constituents of the ginger oleoresin ( Zingiber officinale Roscoe) have been shown to mediate anti-tumour activity and to contribute to the anti-inflammatory, antioxidant, antimicrobial, and antiemetic properties of ginger. Here we report on the inhibitory properties of [10]-Gingerol against metastatic triple negative breast cancer (TNBC) in vitro and in vivo . We show that [10]-Gingerol concentration-dependently induces apoptotic death in mouse and human TNBC cell lines in vitro . In addition, [10]-Gingerol is well tolerated in vivo , induces a marked increase in caspase-3 activation and inhibits orthotopic tumour growth in a syngeneic mouse model of spontaneous breast cancer metastasis. Importantly, using both spontaneous and experimental metastasis assays, we show for the first time that [10]-Gingerol significantly inhibits metastasis to multiple organs including lung, bone and brain. Remarkably, inhibition of brain metastasis was observed even when treatment was initiated after surgical removal of the primary tumour. Taken together, these results indicate that [10]-Gingerol may be a safe and useful complementary therapy for the treatment of metastatic breast cancer and warrant further investigation of its efficacy, either alone or in combination with standard systemic therapies, in pre-clinical models of metastatic breast cancer and in patients.
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abstract b40 10 Gingerol as a pro apoptotic molecule in triple negative breast cancer
Molecular Cancer Research, 2017Co-Authors: Ana Carolina Baptista Moreno Martin, Angelina Maria Fuzer, Rebeka Tomasin, Amanda Blanque Becceneri, Paulo C Vieira, Marcia R CominettiAbstract:The aim of this work was to study the pro-apoptotic effects of [10]-Gingerol and connect them to anti-tumor and anti-metastatic activities in triple negative breast cancer (TNBC) cell lines and in an spontaneous triple negative breast cancer model in vivo. Breast cancer has the highest incidence among women and metastasis is the major cause of death in cancer. TNBC affects 20% of women with breast cancer. This cancer type is very aggressive and has a high propensity to form lung and brain metastases. Nowadays, there is no effective treatment for TNBC and therefore, new therapies are required. Studies to discovery new molecules to be used in more efficient treatments for this disease are essential. Molecules that can interfere with cell proliferation, migration, invasion, apoptosis and cell cycle can be used as a model or tools to develop new anti-metastatic drugs. Epidemiologic studies have shown that Asian populations have lower incidence of breast cancer comparing to western populations. This has been attributed in part to differences in dietary habits. In particular, Gingerols, natural compounds extracted from ginger rhizomes, have been shown to present anti-cancer properties against various tumor cell types in vitro and in vivo. MTT assay was performed to verify the inhibitory effects of [10]-Gingerol on cell proliferation. To investigate [10]-Gingerol mechanisms of action, apoptosis, cell cycle assays and TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) were performed. For the in vivo data an spontaneous model of breast cancer metastasis was used. Results : [10]-Gingerol was able to inhibit cell proliferation in different cell lines. In the murine cell line (4T1Br4), [10]-Gingerol induced apoptosis, cell cycle arrest at sub-G0 phase and also induced DNA damage demonstrated by TUNEL assay, therefore interfering with DNA and provoking its damage. [10]-Gingerol inhibited lung, bone and brain metastases in an intra-mammary fat pad spontaneous breast cancer model. Conclusion : [10]-Gingerol showed to be a non-toxic compound with anti-proliferative and DNA damaging effects, inducing cell apoptosis in vitro and also inhibiting lung, bone and brain metastases in a spontaneous TNBC model in vivo. Patent deposit: BR 10 2015 024093 7. Approved by ethical committee – E507 and 3224-1. Citation Format: Ana Carolina B. M. Martin, Rebeka Tomasin, Amanda Blanque Becceneri, Angelina Fuzer, Paulo Cezar Vieira, Marcia Regina Cominetti. [10]-Gingerol as a pro-apoptotic molecule in triple negative breast cancer [abstract]. In: Proceedings of the AACR Special Conference on DNA Repair: Tumor Development and Therapeutic Response; 2016 Nov 2-5; Montreal, QC, Canada. Philadelphia (PA): AACR; Mol Cancer Res 2017;15(4_Suppl):Abstract nr B40.
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Purification and differential biological effects of ginger-derived substances on normal and tumor cell lines
Journal of Chromatography B, 2012Co-Authors: James Almada Da Silva, Ana Carolina Baptista Moreno Martin, Amanda Blanque Becceneri, Paulo C Vieira, Hêmily Sanches Mutti, Maria Fátima Das Graças Fernandes Da Silva, João B. Fernandes, Marcia R CominettiAbstract:Abstract This study describes an optimization of [6]-, [8]- and [10]-Gingerol isolation and purification in semi-preparative HPLC scale and their anti-proliferative activity. The Gingerols purification was carried out in HPLC system using a Luna-C18 and the best mobile phase evaluated was MeOH/H2O (75:25, v/v). This new methodology for the Gingerols isolation was very effective, since considerable amounts (in the range of milligrams) with a good purity degree (∼98%) were achieved in 30 min of chromatographic run. [6]-, [8]- and [10]-Gingerol purified by this methodology inhibited the proliferation of MDA-MB-231 tumor cell line with IC50 of 666.2 ± 134.6 μM, 135.6 ± 22.6 μM and 12.1 ± 0.3 μM, respectively. These substances also inhibited human fibroblasts (HF) cell proliferation, however in concentrations starting from 500 μM. In conclusion, our results demonstrate an optimization of Gingerols isolation and their specific anti-proliferative activities against tumor cells, suggesting their use as important models for drug design in an attempt to develop new compounds with fewer side effects when compared to conventional chemotherapy.
