The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Zhenzhou Jiang - One of the best experts on this subject based on the ideXlab platform.

  • Synergistic anti-cancer effect of Pristimerin and docetaxel on human colorectal HCT-116 cells
    Synergy, 2020
    Co-Authors: Bashir A. Yousef, Luyong Zhang, Hozeifa M. Hassan, Muhanad Elhafiz, Zhenzhou Jiang
    Abstract:

    Abstract Pristimerin is a quinonemethide triterpenoid compound that exerts anticancer activities against different cancer cells, including colorectal cancer. The current study aimed to study the cytotoxic and apoptosis-inducing effects of Pristimerin alone or in combination with docetaxel on HCT-116 human colorectal cancer cell line. The cytotoxicity of Pristimerin, or docetaxel, or the combination on HCT-116 cells were measured using the MTT method. The combination index (CI) was calculated using the isobologram method of Chou and Talalay. Annexin V/PI double staining was used to assess the apoptosis-inducing effect of these agents. Our results showed that both Pristimerin and docetaxel showed potent cytotoxic effects against HCT-116 cells in dose-dependent manners. Moreover, the efficacy of docetaxel combined Pristimerin was significantly increased, compared to individual treatment. The CI value was (0.55 to 0.89) that indicated the synergistic interaction between two agents to inhibit cell growth of CRC cells. Furthermore, Annexin V/PI assay showed that both agents induced apoptosis in HCT-116 in cancer cells. While treatment with combination resulted in a significant enhancement in apoptosis rates compared to individual treatment. Collectively, the data indicated that Pristimerin potentiated the anticancer activities of docetaxel in colon cancer cells by reducing cell viability and promoting apoptosis.

  • Pristimerin exhibits in vitro and in vivo anticancer activities through inhibition of nuclear factor-кB signaling pathway in colorectal cancer cells.
    Phytomedicine : international journal of phytotherapy and phytopharmacology, 2018
    Co-Authors: Bashir A. Yousef, Luyong Zhang, Hozeifa M. Hassan, Zhenzhou Jiang
    Abstract:

    Abstract Background Colorectal cancer (CRC) is one of the most common malignancies associated with high mortality rate worldwide. We previously reported that Pristimerin inhibits cell growth and induces apoptosis in CRC cells. Hypothesis/Purpose To further understand the molecular mechanism by which Pristimerin elicits its anticancer activities on colon cancer cells, we investigated its effect on nuclear factor-κB (NF-κB) signaling pathway. Study Design This study consisted of both in vitro and in vivo experiments involving HCT-116 cell line and xenograft mouse model. Molecular techniques such as qRT-PCR, western blotting and immunofluorescence were used to demonstrate Pristimerin in vitro effect on NF-κB signaling pathway; whereas it's in vivo activity was analyzed by western blot and immunohistochemistry on tumor tissues. Results Our in vitro results on HCT-116 cells showed that Pristimerin inhibited IKK phosphorylation, IкB-α degradations and IкB-α phosphorylation in both dose- and time- dependent manners, which caused suppression of NF-кB p65 phosphorylation, nuclear translocation and accumulation of NF-кB. Moreover, Pristimerin was found to inhibit both constitutive activated-NF-кB and tumor necrosis factor-α (TNF-α)- and lipopolysaccharide (LPS)-induced activation of NF-кB signaling pathway. Furthermore, our in vivo results on xenograft animal model revealed that Pristimerin inhibited tumor growth mainly through suppressing NF-кB activity in tumor tissues. Conclusion Pristimerin antitumor activities were mainly mediated through inhibition of NF-кB signaling pathway in colon tumor cells. These findings further explain that Pristimerin has the therapeutic potential for targeting colon cancer.

  • Anticancer Potential and Molecular Targets of Pristimerin: A Mini- Review.
    Current cancer drug targets, 2017
    Co-Authors: Bashir A. Yousef, Luyong Zhang, Hozeifa M. Hassan, Zhenzhou Jiang
    Abstract:

    Pristimerin, a natural triterpenoid isolated form Celastrus and Maytenus spp, has been shown to possess a variety of biological and pharmacological effects. Recently, Pristimerin has attracted more attention, especially for its potential anticancer activities. The anticancer activities of Pristimerin have been illustrated in various cancer cell lines and animal models. It has been found to inhibit in vitro and in vivo proliferation, survival, angiogenesis and metastasis of tumor cells. These activities have been attributed to its modulation of various molecular targets such as cyclins, apoptosis- related proteins, proteasome activity, reactive oxygen species, as well as NF-kB, AKT/mTOR and MAPK/ERK pathways. This mini-review discussed the cellular impact and animal studies of Pristimerin treatment, with more attention on the various molecular targets of Pristimerin.

  • Pristimerin inhibits proliferation, migration and invasion, and induces apoptosis in HCT-116 colorectal cancer cells.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2016
    Co-Authors: Bashir A. Yousef, Luyong Zhang, Hozeifa M. Hassan, Mounia Guerram, Aida Mejda Hamdi, Bin Wang, Zhenzhou Jiang
    Abstract:

    Colorectal cancer (CRC) is one of the world's most common cancers with a high mortality rate mainly due to metastasis. Our previous study showed that Pristimerin had potent antitumor activities against human CRC cells. In the present study, we further evaluated Pristimerin anti-tumor and anti-metastatic properties. MTT assay, Hoechst staining, Annexin V/PI double staining, reactive oxygen species (ROS) measurements were used to assess Pristimerin cytotoxicity and apoptotic-inducing effects on HCT-116 cells. Wound healing assay and Transwell assay were used to estimate Pristimerin anti-migration and anti-invasion activities on CRC cells. Meanwhile, HCT-116 xenograft model applied for investigating in vivo antitumor activities. Our results showed that Pristimerin mediated in vitro HCT-116 cell death, through generation of intracellular ROS and apoptosis induction. Tumor volumes and weights measurements, pathological analysis and Tunnel assay proved that Pristimerin inhibited in vivo HCT-116 xenografts growth. Pristimerin was also able to limit CRC invasion and metastasis. It caused downregulation of PI3K/AKT/mTOR pathway and its subsequent downstream p70S6K and E4-BP1 proteins. Collectively, Pristimerin exerted both in vitro and in vivo cytotoxic and anti-metastatic effects on HCT-116 cells, suggesting that Pristimerin has potential as a new anticancer drug for treatment of colon cancer.

  • Pristimerin demonstrates anticancer potential in colorectal cancer cells by inducing G1 phase arrest and apoptosis and suppressing various pro-survival signaling proteins.
    Oncology reports, 2015
    Co-Authors: Bashir A. Yousef, Luyong Zhang, Hozeifa M. Hassan, Mounia Guerram, Aida Mejda Hamdi, Zhenzhou Jiang
    Abstract:

    Pristimerin is a naturally occurring triterpenoid that has a cytotoxic effect on several cancer cell lines. However, the cytotoxic effects of Pristimerin as well as its molecular mechanisms of action against colorectal cancer have never been explored. In the present study, we investigated the anticancer potential of Pristimerin, and examined the different signaling pathways affected by its action in three colon cancer cell lines namely HCT-116, COLO-205 and SW-620. Pristimerin was found to possess potent cytotoxic and proliferation inhibitory effects against these cell lines. Cell cycle analysis revealed G1 phase arrest, which was strongly associated with decreased expression of cyclin D1 and cyclin-dependent kinases (cdk4 and cdk6) with concomitant induction of p21. Pristimerin also induced apoptosis in a dose-dependent manner. Cell plasma membrane alterations studied by Annexin V/PI double staining, loss of mitochondrial membrane potential (ΔΨm), measurements of caspase activities and the inhibitory effect of Z-VAD-FMK (a caspase inhibitor) confirmed the apoptotic effect of Pristimerin. Moreover, western blot data showed that apoptotic induction was associated with activated caspase-3 and -8, PARP-1 cleavage and modulation of the expression levels of Bcl-2 family proteins. Additionally, Pristimerin treatment downregulated the phosphorylated forms of EGFR and HER2 proteins, and subsequently caused a decrease in the phosphorylated forms of Erk1/2, Akt, mTOR and NF-κB proteins. Taken together, these results suggest that Pristimerin may have potential as a new targeting therapeutic strategy for the treatment of colon cancer.

Luyong Zhang - One of the best experts on this subject based on the ideXlab platform.

  • Synergistic anti-cancer effect of Pristimerin and docetaxel on human colorectal HCT-116 cells
    Synergy, 2020
    Co-Authors: Bashir A. Yousef, Luyong Zhang, Hozeifa M. Hassan, Muhanad Elhafiz, Zhenzhou Jiang
    Abstract:

    Abstract Pristimerin is a quinonemethide triterpenoid compound that exerts anticancer activities against different cancer cells, including colorectal cancer. The current study aimed to study the cytotoxic and apoptosis-inducing effects of Pristimerin alone or in combination with docetaxel on HCT-116 human colorectal cancer cell line. The cytotoxicity of Pristimerin, or docetaxel, or the combination on HCT-116 cells were measured using the MTT method. The combination index (CI) was calculated using the isobologram method of Chou and Talalay. Annexin V/PI double staining was used to assess the apoptosis-inducing effect of these agents. Our results showed that both Pristimerin and docetaxel showed potent cytotoxic effects against HCT-116 cells in dose-dependent manners. Moreover, the efficacy of docetaxel combined Pristimerin was significantly increased, compared to individual treatment. The CI value was (0.55 to 0.89) that indicated the synergistic interaction between two agents to inhibit cell growth of CRC cells. Furthermore, Annexin V/PI assay showed that both agents induced apoptosis in HCT-116 in cancer cells. While treatment with combination resulted in a significant enhancement in apoptosis rates compared to individual treatment. Collectively, the data indicated that Pristimerin potentiated the anticancer activities of docetaxel in colon cancer cells by reducing cell viability and promoting apoptosis.

  • Pristimerin exhibits in vitro and in vivo anticancer activities through inhibition of nuclear factor-кB signaling pathway in colorectal cancer cells.
    Phytomedicine : international journal of phytotherapy and phytopharmacology, 2018
    Co-Authors: Bashir A. Yousef, Luyong Zhang, Hozeifa M. Hassan, Zhenzhou Jiang
    Abstract:

    Abstract Background Colorectal cancer (CRC) is one of the most common malignancies associated with high mortality rate worldwide. We previously reported that Pristimerin inhibits cell growth and induces apoptosis in CRC cells. Hypothesis/Purpose To further understand the molecular mechanism by which Pristimerin elicits its anticancer activities on colon cancer cells, we investigated its effect on nuclear factor-κB (NF-κB) signaling pathway. Study Design This study consisted of both in vitro and in vivo experiments involving HCT-116 cell line and xenograft mouse model. Molecular techniques such as qRT-PCR, western blotting and immunofluorescence were used to demonstrate Pristimerin in vitro effect on NF-κB signaling pathway; whereas it's in vivo activity was analyzed by western blot and immunohistochemistry on tumor tissues. Results Our in vitro results on HCT-116 cells showed that Pristimerin inhibited IKK phosphorylation, IкB-α degradations and IкB-α phosphorylation in both dose- and time- dependent manners, which caused suppression of NF-кB p65 phosphorylation, nuclear translocation and accumulation of NF-кB. Moreover, Pristimerin was found to inhibit both constitutive activated-NF-кB and tumor necrosis factor-α (TNF-α)- and lipopolysaccharide (LPS)-induced activation of NF-кB signaling pathway. Furthermore, our in vivo results on xenograft animal model revealed that Pristimerin inhibited tumor growth mainly through suppressing NF-кB activity in tumor tissues. Conclusion Pristimerin antitumor activities were mainly mediated through inhibition of NF-кB signaling pathway in colon tumor cells. These findings further explain that Pristimerin has the therapeutic potential for targeting colon cancer.

  • Anticancer Potential and Molecular Targets of Pristimerin: A Mini- Review.
    Current cancer drug targets, 2017
    Co-Authors: Bashir A. Yousef, Luyong Zhang, Hozeifa M. Hassan, Zhenzhou Jiang
    Abstract:

    Pristimerin, a natural triterpenoid isolated form Celastrus and Maytenus spp, has been shown to possess a variety of biological and pharmacological effects. Recently, Pristimerin has attracted more attention, especially for its potential anticancer activities. The anticancer activities of Pristimerin have been illustrated in various cancer cell lines and animal models. It has been found to inhibit in vitro and in vivo proliferation, survival, angiogenesis and metastasis of tumor cells. These activities have been attributed to its modulation of various molecular targets such as cyclins, apoptosis- related proteins, proteasome activity, reactive oxygen species, as well as NF-kB, AKT/mTOR and MAPK/ERK pathways. This mini-review discussed the cellular impact and animal studies of Pristimerin treatment, with more attention on the various molecular targets of Pristimerin.

  • Pristimerin inhibits proliferation, migration and invasion, and induces apoptosis in HCT-116 colorectal cancer cells.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2016
    Co-Authors: Bashir A. Yousef, Luyong Zhang, Hozeifa M. Hassan, Mounia Guerram, Aida Mejda Hamdi, Bin Wang, Zhenzhou Jiang
    Abstract:

    Colorectal cancer (CRC) is one of the world's most common cancers with a high mortality rate mainly due to metastasis. Our previous study showed that Pristimerin had potent antitumor activities against human CRC cells. In the present study, we further evaluated Pristimerin anti-tumor and anti-metastatic properties. MTT assay, Hoechst staining, Annexin V/PI double staining, reactive oxygen species (ROS) measurements were used to assess Pristimerin cytotoxicity and apoptotic-inducing effects on HCT-116 cells. Wound healing assay and Transwell assay were used to estimate Pristimerin anti-migration and anti-invasion activities on CRC cells. Meanwhile, HCT-116 xenograft model applied for investigating in vivo antitumor activities. Our results showed that Pristimerin mediated in vitro HCT-116 cell death, through generation of intracellular ROS and apoptosis induction. Tumor volumes and weights measurements, pathological analysis and Tunnel assay proved that Pristimerin inhibited in vivo HCT-116 xenografts growth. Pristimerin was also able to limit CRC invasion and metastasis. It caused downregulation of PI3K/AKT/mTOR pathway and its subsequent downstream p70S6K and E4-BP1 proteins. Collectively, Pristimerin exerted both in vitro and in vivo cytotoxic and anti-metastatic effects on HCT-116 cells, suggesting that Pristimerin has potential as a new anticancer drug for treatment of colon cancer.

  • Pristimerin demonstrates anticancer potential in colorectal cancer cells by inducing G1 phase arrest and apoptosis and suppressing various pro-survival signaling proteins.
    Oncology reports, 2015
    Co-Authors: Bashir A. Yousef, Luyong Zhang, Hozeifa M. Hassan, Mounia Guerram, Aida Mejda Hamdi, Zhenzhou Jiang
    Abstract:

    Pristimerin is a naturally occurring triterpenoid that has a cytotoxic effect on several cancer cell lines. However, the cytotoxic effects of Pristimerin as well as its molecular mechanisms of action against colorectal cancer have never been explored. In the present study, we investigated the anticancer potential of Pristimerin, and examined the different signaling pathways affected by its action in three colon cancer cell lines namely HCT-116, COLO-205 and SW-620. Pristimerin was found to possess potent cytotoxic and proliferation inhibitory effects against these cell lines. Cell cycle analysis revealed G1 phase arrest, which was strongly associated with decreased expression of cyclin D1 and cyclin-dependent kinases (cdk4 and cdk6) with concomitant induction of p21. Pristimerin also induced apoptosis in a dose-dependent manner. Cell plasma membrane alterations studied by Annexin V/PI double staining, loss of mitochondrial membrane potential (ΔΨm), measurements of caspase activities and the inhibitory effect of Z-VAD-FMK (a caspase inhibitor) confirmed the apoptotic effect of Pristimerin. Moreover, western blot data showed that apoptotic induction was associated with activated caspase-3 and -8, PARP-1 cleavage and modulation of the expression levels of Bcl-2 family proteins. Additionally, Pristimerin treatment downregulated the phosphorylated forms of EGFR and HER2 proteins, and subsequently caused a decrease in the phosphorylated forms of Erk1/2, Akt, mTOR and NF-κB proteins. Taken together, these results suggest that Pristimerin may have potential as a new targeting therapeutic strategy for the treatment of colon cancer.

Jingxuan Pan - One of the best experts on this subject based on the ideXlab platform.

  • Pristimerin targeting NF‐κB pathway inhibits proliferation, migration, and invasion in esophageal squamous cell carcinoma cells
    Cell biochemistry and function, 2018
    Co-Authors: Fuxing Tan, Jingfeng Zhou, Jingxuan Pan
    Abstract:

    Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer-related death with poor prognosis in China. Identifying novel targeted therapies in ESCC is urgently needed. The aberrant activation of NF-κB signalling pathway is critical for prognosis and recurrence of ESCC, which make it a potential target in the treatment of ESCC. Here, we found that Pristimerin inhibited ESCC cell proliferation, migration, invasion, induced cell apoptosis, and eliminated cancer stem-like cells (CSCs). It also showed a synergistic effect on ESCC when combined with 5-fluorouracil (5-FU). Moreover, Pristimerin potently inhibited the growth of ESCC xenograft in nude mice. The anti-ESCC effects of Pristimerin were demonstrated to be associated with the inhibition of NF-κB pathway by suppressing tumour necrosis factor α (TNFα)-induced IκBα phosphorylation, p65 translocation, and NF-κB-dependent gene expression. This study provides an evidence for the development of Pristimerin to be a new therapeutic agent for ESCC. SIGNIFICANCE OF THE STUDY Although several approaches including surgery, chemotherapy, and radiotherapy had been applied in the treatment of ESCC, more effective targeted chemotherapies are required to increase the survival rates of patients. This study suggested that inhibiting NF-κB signalling pathway could be an effective approach for the treatment of ESCC. Pristimerin, a potent NF-κB inhibitor, exerted potent anti-ESCC effects both in vitro and in vivo, which may be a promising therapeutic agent for ESCC.

  • Pristimerin effectively inhibits the malignant phenotypes of uveal melanoma cells by targeting NF‑κB pathway.
    International journal of oncology, 2017
    Co-Authors: Biao Zhang, Jing Zhang, Jingxuan Pan
    Abstract:

    Uveal melanoma (UM) is a highly aggressive intraocular malignancy that lacks any effective targeted-therapy. Neither survival nor prognosis has been improved for the past decades in patients with metastatic UM. NF‑κB pathway is reported to be abnormally activated in UM. However, the role of NF‑κB pathway as a potential therapeutical target in UM remains unclear. Here, the effect of Pristimerin, a potent inhibitor of NF‑κB pathway, on UM cells in terms of growth, apoptosis, motility, invasion and cancer stem-like cells (CSCs) was evaluated in vitro. We showed that Pristimerin suppressed tumor necrosis factor α (TNFα)-induced IκBα phosphorylation, translocation of p65, and expression of NF‑κB-dependent genes. Moreover, Pristimerin decreased cell viability and clonogenic ability of UM cells. A synergistic effect was observed in the treatment of Pristimerin combined with vinblastine, a frontline therapeutic agent, in UM. Pristimerin led to a significant increase in the Annexin V+ cell population as measured by flow cytometry. We also observed that Pristimerin impaired the abilities of migration and invasion in UM cells. Furthermore, Pristimerin eliminated the ALDH+ cells and weakened serial re-plating ability of melanosphere. Collectively, Pristimerin shows remarkable anticancer activities in UM cells through inactivating NF‑κB pathway, revealing that Pristimerin may be a promising therapeutic agent in UM.

Bashir A. Yousef - One of the best experts on this subject based on the ideXlab platform.

  • Synergistic anti-cancer effect of Pristimerin and docetaxel on human colorectal HCT-116 cells
    Synergy, 2020
    Co-Authors: Bashir A. Yousef, Luyong Zhang, Hozeifa M. Hassan, Muhanad Elhafiz, Zhenzhou Jiang
    Abstract:

    Abstract Pristimerin is a quinonemethide triterpenoid compound that exerts anticancer activities against different cancer cells, including colorectal cancer. The current study aimed to study the cytotoxic and apoptosis-inducing effects of Pristimerin alone or in combination with docetaxel on HCT-116 human colorectal cancer cell line. The cytotoxicity of Pristimerin, or docetaxel, or the combination on HCT-116 cells were measured using the MTT method. The combination index (CI) was calculated using the isobologram method of Chou and Talalay. Annexin V/PI double staining was used to assess the apoptosis-inducing effect of these agents. Our results showed that both Pristimerin and docetaxel showed potent cytotoxic effects against HCT-116 cells in dose-dependent manners. Moreover, the efficacy of docetaxel combined Pristimerin was significantly increased, compared to individual treatment. The CI value was (0.55 to 0.89) that indicated the synergistic interaction between two agents to inhibit cell growth of CRC cells. Furthermore, Annexin V/PI assay showed that both agents induced apoptosis in HCT-116 in cancer cells. While treatment with combination resulted in a significant enhancement in apoptosis rates compared to individual treatment. Collectively, the data indicated that Pristimerin potentiated the anticancer activities of docetaxel in colon cancer cells by reducing cell viability and promoting apoptosis.

  • Pristimerin exhibits in vitro and in vivo anticancer activities through inhibition of nuclear factor-кB signaling pathway in colorectal cancer cells.
    Phytomedicine : international journal of phytotherapy and phytopharmacology, 2018
    Co-Authors: Bashir A. Yousef, Luyong Zhang, Hozeifa M. Hassan, Zhenzhou Jiang
    Abstract:

    Abstract Background Colorectal cancer (CRC) is one of the most common malignancies associated with high mortality rate worldwide. We previously reported that Pristimerin inhibits cell growth and induces apoptosis in CRC cells. Hypothesis/Purpose To further understand the molecular mechanism by which Pristimerin elicits its anticancer activities on colon cancer cells, we investigated its effect on nuclear factor-κB (NF-κB) signaling pathway. Study Design This study consisted of both in vitro and in vivo experiments involving HCT-116 cell line and xenograft mouse model. Molecular techniques such as qRT-PCR, western blotting and immunofluorescence were used to demonstrate Pristimerin in vitro effect on NF-κB signaling pathway; whereas it's in vivo activity was analyzed by western blot and immunohistochemistry on tumor tissues. Results Our in vitro results on HCT-116 cells showed that Pristimerin inhibited IKK phosphorylation, IкB-α degradations and IкB-α phosphorylation in both dose- and time- dependent manners, which caused suppression of NF-кB p65 phosphorylation, nuclear translocation and accumulation of NF-кB. Moreover, Pristimerin was found to inhibit both constitutive activated-NF-кB and tumor necrosis factor-α (TNF-α)- and lipopolysaccharide (LPS)-induced activation of NF-кB signaling pathway. Furthermore, our in vivo results on xenograft animal model revealed that Pristimerin inhibited tumor growth mainly through suppressing NF-кB activity in tumor tissues. Conclusion Pristimerin antitumor activities were mainly mediated through inhibition of NF-кB signaling pathway in colon tumor cells. These findings further explain that Pristimerin has the therapeutic potential for targeting colon cancer.

  • Anticancer Potential and Molecular Targets of Pristimerin: A Mini- Review.
    Current cancer drug targets, 2017
    Co-Authors: Bashir A. Yousef, Luyong Zhang, Hozeifa M. Hassan, Zhenzhou Jiang
    Abstract:

    Pristimerin, a natural triterpenoid isolated form Celastrus and Maytenus spp, has been shown to possess a variety of biological and pharmacological effects. Recently, Pristimerin has attracted more attention, especially for its potential anticancer activities. The anticancer activities of Pristimerin have been illustrated in various cancer cell lines and animal models. It has been found to inhibit in vitro and in vivo proliferation, survival, angiogenesis and metastasis of tumor cells. These activities have been attributed to its modulation of various molecular targets such as cyclins, apoptosis- related proteins, proteasome activity, reactive oxygen species, as well as NF-kB, AKT/mTOR and MAPK/ERK pathways. This mini-review discussed the cellular impact and animal studies of Pristimerin treatment, with more attention on the various molecular targets of Pristimerin.

  • Pristimerin inhibits proliferation, migration and invasion, and induces apoptosis in HCT-116 colorectal cancer cells.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2016
    Co-Authors: Bashir A. Yousef, Luyong Zhang, Hozeifa M. Hassan, Mounia Guerram, Aida Mejda Hamdi, Bin Wang, Zhenzhou Jiang
    Abstract:

    Colorectal cancer (CRC) is one of the world's most common cancers with a high mortality rate mainly due to metastasis. Our previous study showed that Pristimerin had potent antitumor activities against human CRC cells. In the present study, we further evaluated Pristimerin anti-tumor and anti-metastatic properties. MTT assay, Hoechst staining, Annexin V/PI double staining, reactive oxygen species (ROS) measurements were used to assess Pristimerin cytotoxicity and apoptotic-inducing effects on HCT-116 cells. Wound healing assay and Transwell assay were used to estimate Pristimerin anti-migration and anti-invasion activities on CRC cells. Meanwhile, HCT-116 xenograft model applied for investigating in vivo antitumor activities. Our results showed that Pristimerin mediated in vitro HCT-116 cell death, through generation of intracellular ROS and apoptosis induction. Tumor volumes and weights measurements, pathological analysis and Tunnel assay proved that Pristimerin inhibited in vivo HCT-116 xenografts growth. Pristimerin was also able to limit CRC invasion and metastasis. It caused downregulation of PI3K/AKT/mTOR pathway and its subsequent downstream p70S6K and E4-BP1 proteins. Collectively, Pristimerin exerted both in vitro and in vivo cytotoxic and anti-metastatic effects on HCT-116 cells, suggesting that Pristimerin has potential as a new anticancer drug for treatment of colon cancer.

  • Pristimerin demonstrates anticancer potential in colorectal cancer cells by inducing G1 phase arrest and apoptosis and suppressing various pro-survival signaling proteins.
    Oncology reports, 2015
    Co-Authors: Bashir A. Yousef, Luyong Zhang, Hozeifa M. Hassan, Mounia Guerram, Aida Mejda Hamdi, Zhenzhou Jiang
    Abstract:

    Pristimerin is a naturally occurring triterpenoid that has a cytotoxic effect on several cancer cell lines. However, the cytotoxic effects of Pristimerin as well as its molecular mechanisms of action against colorectal cancer have never been explored. In the present study, we investigated the anticancer potential of Pristimerin, and examined the different signaling pathways affected by its action in three colon cancer cell lines namely HCT-116, COLO-205 and SW-620. Pristimerin was found to possess potent cytotoxic and proliferation inhibitory effects against these cell lines. Cell cycle analysis revealed G1 phase arrest, which was strongly associated with decreased expression of cyclin D1 and cyclin-dependent kinases (cdk4 and cdk6) with concomitant induction of p21. Pristimerin also induced apoptosis in a dose-dependent manner. Cell plasma membrane alterations studied by Annexin V/PI double staining, loss of mitochondrial membrane potential (ΔΨm), measurements of caspase activities and the inhibitory effect of Z-VAD-FMK (a caspase inhibitor) confirmed the apoptotic effect of Pristimerin. Moreover, western blot data showed that apoptotic induction was associated with activated caspase-3 and -8, PARP-1 cleavage and modulation of the expression levels of Bcl-2 family proteins. Additionally, Pristimerin treatment downregulated the phosphorylated forms of EGFR and HER2 proteins, and subsequently caused a decrease in the phosphorylated forms of Erk1/2, Akt, mTOR and NF-κB proteins. Taken together, these results suggest that Pristimerin may have potential as a new targeting therapeutic strategy for the treatment of colon cancer.

Hyo-jeong Lee - One of the best experts on this subject based on the ideXlab platform.

  • Anti-cancer effect of Pristimerin by inhibition of HIF-1α involves the SPHK-1 pathway in hypoxic prostate cancer cells
    BMC cancer, 2016
    Co-Authors: Seon-ok Lee, Joo-seok Kim, Myoung-sun Lee, Hyo-jeong Lee
    Abstract:

    Hypoxia is a typical character of locally advanced solid tumours. The transcription factor hypoxia-inducible factor 1α (HIF-1α) is the main regulator under the hypoxic environment. HIF-1α regulates various genes to enhance tumour progression, angiogenesis, and metastasis. Sphingosine kinase 1 (SPHK-1) is a modulator of HIF-1α. To investigate the molecular mechanisms of Pristimerin in association with SPHK-1 pathways in hypoxic PC-3 cancer cells. Vascular endothelial growth factor (VEGF) production, cell cycles, and SPHK-1 activity were measured, and western blotting, an MTT assay, and an RNA interference assay were performed. Pristimerin inhibited HIF-1α accumulation in a concentration- and-time-dependent manner in hypoxic PC-3 cells. Pristimerin suppressed the expression of HIF-1α by inhibiting SPHK-1. Moreover, inhibiting SPHK-1 with a sphingosine kinase inhibitor enhanced the suppression of HIF-1α, phosphorylation AKT, and glycogen synthase kinase-3β (GSK-3β) by Pristimerin under hypoxia. Furthermore, a reactive oxygen species (ROS) scavenger enhanced the inhibition of HIF-1α and SPHK-1 by Pristimerin. Taken together, these findings suggest that Pristimerin can exert an anti-cancer activity by inhibiting HIF-1α through the SPHK-1 pathway.

  • Additional file 1: Figure S1. of Anti-cancer effect of Pristimerin by inhibition of HIF-1α involves the SPHK-1 pathway in hypoxic prostate cancer cells
    2016
    Co-Authors: Seon-ok Lee, Joo-seok Kim, Myoung-sun Lee, Hyo-jeong Lee
    Abstract:

    Pristimerin does not affect PI3K in PC-3 cells under hypoxia. PC-3 cells were treated with Pristimerin (1 μM) and or SPHK-1 inhibitor (SKI) (10 μM) for 4 h under hypoxia. Effect of Pristimerin on the expression of PI3K in hypoxic PC-3 cells. Western blotting was performed to determine the expression of PI3K and β-actin in hypoxic PC-3 cells. (TIF 66 kb