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Jack L Arbiser - One of the best experts on this subject based on the ideXlab platform.

  • Honokiol bis dichloroacetate Honokiol dca demonstrates activity in vemurafenib resistant melanoma in vivo
    Oncotarget, 2016
    Co-Authors: Michael Y Bonner, Isabella Karlsson, Monica Rodolfo, Rebecca S Arnold, Elisabetta Vergani, Jack L Arbiser
    Abstract:

    The majority of human melanomas bears BRAF mutations and thus is treated with inhibitors of BRAF, such as vemurafenib. While patients with BRAF mutations often demonstrate an initial dramatic response to vemurafenib, relapse is extremely common. Thus, novel agents are needed for the treatment of these aggressive melanomas. Honokiol is a small molecule compound derived from Magnolia grandiflora that has activity against solid tumors and hematopoietic neoplasms. In order to increase the lipophilicity of Honokiol, we have synthesized Honokiol DCA, the dichloroacetate ester of Honokiol. In addition, we synthesized a novel fluorinated Honokiol analog, bis-trifluoromethyl-bis-(4-hydroxy-3-allylphenyl) methane (hexafluoro). Both compounds exhibited activity against A375 melanoma in vivo, but Honokiol DCA was more active. Gene arrays comparing treated with vehicle control tumors demonstrated induction of the respiratory enzyme succinate dehydrogenase B (SDHB) by treatment, suggesting that our Honokiol analogs induce respiration in vivo. We then examined its effect against a pair of melanomas, LM36 and LM36R, in which LM36R differs from LM36 in that LM36R has acquired vemurafenib resistance. Honokiol DCA demonstrated in vivo activity against LM36R (vemurafenib resistant) but not against parental LM36. Honokiol DCA and hexafluoro inhibited the phosphorylation of DRP1, thus stimulating a phenotype suggestive of respiration through mitochondrial normalization. Honokiol DCA may act in vemurafenib resistant melanomas to increase both respiration and reactive oxygen generation, leading to activity against aggressive melanoma in vivo.

  • antimetastatic activity of Honokiol in osteosarcoma
    Cancer, 2012
    Co-Authors: Patrick Steinmann, Jack L Arbiser, Denise K Walters, Matthias J E Arlt, Ingo J Banke, Urs Ziegler, Bettina Langsam, Roman Muff, Walter Born
    Abstract:

    BACKGROUND: Metastasizing osteosarcoma has a mean 5-year survival rate of only 20% to 30%. Therefore, novel chemotherapeutics for more effective treatment of this disease are required. METHODS: The antineoplastic activity of Honokiol, which was demonstrated previously in numerous malignancies, was studied in vivo in C3H mice subcutaneously injected with syngeneic β-galactosidase bacterial gene (lacZ)-expressing LM8 osteosarcoma (LM8-lacZ) cells. In vitro cytotoxic effects of Honokiol were investigated in 8 human and 2 murine osteosarcoma cell lines with different in vivo metastatic potential. RESULTS: Seven days after subcutaneous flank injection of LM8-lacZ cells, daily intraperitoneal treatment of mice with 150 mg/kg Honokiol reduced the number of micrometastases in the lung by 41% and reduced the number of macrometastases in the lung and liver by 69% and 80%, respectively, compared with control. Primary tumor growth was not inhibited. In osteosarcoma cell lines, Honokiol inhibited the metabolic activity with a half-maximal concentration (IC(50) ) between 8.0 μg/mL and 16 μg/mL. Cyclosporin A partially reversed the inhibition of metabolic activity in LM8-lacZ cells. Cell proliferation and wound healing migration of LM8-lacZ cells were inhibited by Honokiol with an IC(50) between 5.0 μg/mL and 10 μg/mL. Higher concentrations caused rapid cell death, which was distinct from necrosis, apoptosis, or autophagy but was associated with swelling of the endoplasmic reticulum, cytoplasmic vacuolation, and morphologically altered mitochondria. CONCLUSIONS: Honokiol exhibited prominent antimetastatic activity in experimental osteosarcoma and caused rapid cell death in vitro that was unrelated to necrosis, apoptosis, or autophagy. The authors concluded that Honokiol has considerable potential for the treatment of metastasizing osteosarcoma.

  • Honokiol activates amp activated protein kinase in breast cancer cells via an lkb1 dependent pathway and inhibits breast carcinogenesis
    Breast Cancer Research, 2012
    Co-Authors: Arumugam Nagalingam, Neeraj K Saxena, Jack L Arbiser, Michael Y Bonner, Dipali Sharma
    Abstract:

    Honokiol, a small-molecule polyphenol isolated from magnolia species, is widely known for its therapeutic potential as an antiinflammatory, antithrombosis, and antioxidant agent, and more recently, for its protective function in the pathogenesis of carcinogenesis. In the present study, we sought to examine the effectiveness of Honokiol in inhibiting migration and invasion of breast cancer cells and to elucidate the underlying molecular mechanisms. Clonogenicity and three-dimensional colony-formation assays were used to examine breast cancer cell growth with Honokiol treatment. The effect of Honokiol on invasion and migration of breast cancer cells was evaluated by using Matrigel invasion, scratch-migration, spheroid-migration, and electric cell-substrate impedance sensing (ECIS)-based migration assays. Western blot and immunofluorescence analysis were used to examine activation of the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) axis. Isogenic LKB1-knockdown breast cancer cell line pairs were developed. Functional importance of AMPK activation and LKB1 overexpression in the biologic effects of Honokiol was examined by using AMPK-null and AMPK-wild type (WT) immortalized mouse embryonic fibroblasts (MEFs) and isogenic LKB1-knockdown cell line pairs. Finally, mouse xenografts, immunohistochemical and Western blot analysis of tumors were used. Analysis of the underlying molecular mechanisms revealed that Honokiol treatment increases AMP-activated protein kinase (AMPK) phosphorylation and activity, as evidenced by increased phosphorylation of the downstream target of AMPK, acetyl-coenzyme A carboxylase (ACC) and inhibition of phosphorylation of p70S6kinase (pS6K) and eukaryotic translation initiation factor 4E binding protein 1 (4EBP1). By using AMPK-null and AMPK-WT (MEFs), we found that AMPK is required for Honokiol-mediated modulation of pACC-pS6K. Intriguingly, we discovered that Honokiol treatment increased the expression and cytoplasmic translocation of tumor-suppressor LKB1 in breast cancer cells. LKB1 knockdown inhibited Honokiol-mediated activation of AMPK and, more important, inhibition of migration and invasion of breast cancer cells. Furthermore, Honokiol treatment resulted in inhibition of breast tumorigenesis in vivo. Analysis of tumors showed significant increases in the levels of cytoplasmic LKB1 and phospho-AMPK in Honokiol-treated tumors. Taken together, these data provide the first in vitro and in vivo evidence of the integral role of the LKB1-AMPK axis in Honokiol-mediated inhibition of the invasion and migration of breast cancer cells. In conclusion, Honokiol treatment could potentially be a rational therapeutic strategy for breast carcinoma.

  • Honokiol inhibits epidermal growth factor receptor signaling and enhances the antitumor effects of epidermal growth factor receptor inhibitors
    Clinical Cancer Research, 2010
    Co-Authors: Rebecca J Leemanneill, Jack L Arbiser, Quan Cai, Sonali Joyce, Sufi M Thomas, Neil E Bhola, Daniel B Neill, Jennifer R Grandis
    Abstract:

    Purpose: This study aimed to investigate the utility of Honokiol, a naturally occurring compound, in the treatment of head and neck squamous cell carcinoma (HNSCC) as well as its ability to target the epidermal growth factor receptor (EGFR), a critical therapeutic target in HNSCC, and to enhance the effects of other EGFR-targeting therapies. Experimental Design: Human HNSCC cell lines and the xenograft animal model of HNSCC were used to test the effects of Honokiol treatment. Results: Honokiol was found to inhibit growth in human HNSCC cell lines, with 50% effective concentration (EC 50 ) values ranging from 3.3 to 7.4 μmol/L, and to induce apoptosis, as shown through Annexin V staining. These effects were associated with inhibition of EGFR signaling, including downstream inhibition of mitogen-activated protein kinase, Akt, and signal transducer and activator of transcription 3 (STAT3), and expression of STAT3 target genes, Bcl-X L and cyclin D1. Furthermore, Honokiol enhanced the growth inhibitory and anti-invasion activity of the EGFR-targeting agent erlotinib. Although HNSCC xenograft models did not show significant inhibition of in vivo tumor growth with Honokiol treatment alone, the combination of Honokiol plus cetuximab, a Food and Drug Administration–approved EGFR inhibitor for this malignancy, significantly enhanced growth inhibition. Finally, HNSCC cells rendered resistant to erlotinib retained sensitivity to the growth inhibitory effects of Honokiol. Conclusions: These results suggest that Honokiol may be an effective therapeutic agent in HNSCC, in which it can augment the effects of EGFR inhibitors and overcome drug resistance. Clin Cancer Res; 16(9); 2571–9. ©2010 AACR.

  • Honokiol a multifunctional antiangiogenic and antitumor agent
    Antioxidants & Redox Signaling, 2009
    Co-Authors: Levi Fried, Jack L Arbiser
    Abstract:

    Abstract Honokiol is a small-molecule polyphenol isolated from the genus Magnolia. It is accompanied by other related polyphenols, including magnolol, with which it shares certain biologic properties. Recently, Honokiol has been found to have antiangiogenic, antiinflammatory, and antitumor properties in preclinical models, without appreciable toxicity. These findings have increased interest in bringing Honokiol to the clinic as a novel chemotherapeutic agent. In addition, mechanistic studies have tried to find the mechanism(s) of action of Honokiol, for two major reasons. First, knowledge of the mechanisms of action may assist development of novel synthetic analogues. Second, mechanistic actions of Honokiol may lead to rational combinations with conventional chemotherapy or radiation for enhanced response to systemic cancers. In this review, we describe the findings that Honokiol has two major mechanisms of action. First, it blocks signaling in tumors with defective p53 function and activated ras by direc...

Shing-hwa Liu - One of the best experts on this subject based on the ideXlab platform.

  • Improved effects of Honokiol on temozolomide-induced autophagy and apoptosis of drug-sensitive and -tolerant glioma cells
    BMC, 2018
    Co-Authors: Chung-ching Chio, Kung-yen Chen, Cheng-kuei Chang, Jian-ying Chuang, Chih-chung Liu, Shing-hwa Liu, Ruei Ming Chen
    Abstract:

    Abstract Background Temozolomide (TMZ)-induced side effects and drug tolerance to human gliomas are still challenging issues now. Our previous studies showed that Honokiol, a major bioactive constituent of Magnolia officinalis (Houpo), is safe for normal brain cells and can kill human glioma cells. This study was further aimed to evaluate the improved effects of Honokiol and TMZ on drug-sensitive and -resistant glioma cells and the possible mechanisms. Methods TMZ-sensitive human U87-MG and murine GL261 glioma cells and TMZ-resistant human U87-MR-R9 glioma cells were exposed to Honokiol and TMZ, and cell viability and LC50 of Honokiol were assayed. To determine the death mechanisms, caspase-3 activity, DNA fragmentation, apoptotic cells, necrotic cells, cell cycle, and autophagic cells. The glioma cells were pretreated with 3-methyladenine (3-MA) and chloroquine (CLQ), two inhibitors of autophagy, and then exposed to Honokiol or TMZ. Results Exposure of human U87-MG glioma cells to Honokiol caused cell death and significantly enhanced TMZ-induced insults. As to the mechanism, combined treatment of human U87-MG cells with Honokiol and TMZ induced greater caspase-3 activation, DNA fragmentation, cell apoptosis, and cell-cycle arrest at the G1 phase but did not affect cell necrosis. The improved effects of Honokiol on TMZ-induced cell insults were further verified in mouse GL261 glioma cells. Moreover, exposure of drug-tolerant human U87-MG-R9 cells to Honokiol induced autophagy and consequent apoptosis. Pretreatments with 3-MA and CLQ caused significant attenuations in Honokiol- and TMZ-induced cell autophagy and apoptosis in human TMZ-sensitive and -tolerant glioma cells. Conclusions Taken together, this study demonstrated the improved effects of Honokiol with TMZ on autophagy and subsequent apoptosis of drug-sensitive and -tolerant glioma cells. Thus, Honokiol has the potential to be a drug candidate for treating human gliomas

  • Calpain/SHP-1 Interaction by Honokiol Dampening Peritoneal Dissemination of Gastric Cancer in nu/nu Mice
    2016
    Co-Authors: Shing-hwa Liu, Keh Bin Wang, Keng Hsin Lan, Wen Jane Lee, Hung Chuan Pan, Yen Chun Peng, Yiching Chen, Chin Chang Shen, Hsuchen Cheng
    Abstract:

    Background: Honokiol, a small-molecular weight natural product, has previously been reported to activate apoptosis and inhibit gastric tumorigenesis. Whether Honokiol inhibits the angiogenesis and metastasis of gastric cancer cells remains unknown. Methodology/Principal Findings: We tested the effects of Honokiol on angiogenic activity and peritoneal dissemination using in vivo, ex vivo and in vitro assay systems. The signaling responses in human gastric cancer cells, human umbilical vascular endothelial cells (HUVECs), and isolated tumors were detected and analyzed. In a xenograft gastric tumor mouse model, Honokiol significantly inhibited the peritoneal dissemination detected by PET/CT technique. Honokiol also effectively attenuated the angiogenesis detected by chick chorioallantoic membrane assay, mouse matrigel plug assay, rat aortic ring endothelial cell sprouting assay, and endothelial cell tube formation assay. Furthermore, Honokiol effectively enhanced signal transducer and activator of transcription (STAT-3) dephosphorylation and inhibited STAT-3 DNA binding activity in human gastric cancer cells and HUVECs, which was correlated with the up-regulation of the activity and protein expressio

  • calpain shp 1 interaction by Honokiol dampening peritoneal dissemination of gastric cancer in nu nu mice
    PLOS ONE, 2012
    Co-Authors: Shing-hwa Liu, Keh Bin Wang, Keng Hsin Lan, Wen Jane Lee, Hung Chuan Pan, Yen Chun Peng, Yiching Chen, Chin Chang Shen, Hsuchen Cheng
    Abstract:

    Background Honokiol, a small-molecular weight natural product, has previously been reported to activate apoptosis and inhibit gastric tumorigenesis. Whether Honokiol inhibits the angiogenesis and metastasis of gastric cancer cells remains unknown. Methodology/Principal Findings We tested the effects of Honokiol on angiogenic activity and peritoneal dissemination using in vivo, ex vivo and in vitro assay systems. The signaling responses in human gastric cancer cells, human umbilical vascular endothelial cells (HUVECs), and isolated tumors were detected and analyzed. In a xenograft gastric tumor mouse model, Honokiol significantly inhibited the peritoneal dissemination detected by PET/CT technique. Honokiol also effectively attenuated the angiogenesis detected by chick chorioallantoic membrane assay, mouse matrigel plug assay, rat aortic ring endothelial cell sprouting assay, and endothelial cell tube formation assay. Furthermore, Honokiol effectively enhanced signal transducer and activator of transcription (STAT-3) dephosphorylation and inhibited STAT-3 DNA binding activity in human gastric cancer cells and HUVECs, which was correlated with the up-regulation of the activity and protein expression of Src homology 2 (SH2)-containing tyrosine phosphatase-1 (SHP-1). Calpain-II inhibitor and siRNA transfection significantly reversed the Honokiol-induced SHP-1 activity. The decreased STAT-3 phosphorylation and increased SHP-1 expression were also shown in isolated peritoneal metastatic tumors. Honokiol was also capable of inhibiting VEGF generation, which could be reversed by SHP-1 siRNA transfection. Conclusions/Significance Honokiol increases expression and activity of SPH-1 that further deactivates STAT3 pathway. These findings also suggest that Honokiol is a novel and potent inhibitor of angiogenesis and peritoneal dissemination of gastric cancer cells, providing support for the application potential of Honokiol in gastric cancer therapy.

  • Honokiol rescues sepsis associated acute lung injury and lethality via the inhibition of oxidative stress and inflammation
    Intensive Care Medicine, 2011
    Co-Authors: Tei Weng, Chia Wei Kuo, Shing-hwa Liu
    Abstract:

    Sepsis has a high mortality rate despite the recent advances in intensive care medicine and antibiotics. Honokiol, a low molecular weight natural product, is known to possess anti-inflammatory activity. Here, we investigate whether Honokiol can ameliorate acute lung injury and lethal response in murine models of sepsis. Mice were intraperitoneally given vehicle or Honokiol 30 min after the induction of sepsis by cecal ligation and puncture (CLP) and endotoxemia by administration of E. coli lipopolysaccharide (LPS). The productions of serum tumor necrosis factor-α (TNF-α), nitric oxide (NO), and high mobility group box 1 (HMGB 1) were increased in mice during sepsis, which could be reversed by Honokiol. Honokiol could also effectively reduce the increased blood lipid peroxidation and nitrotyrosine in septic mice. Honokiol significantly reversed the inductions of inducible NO synthase and nuclear factor-κB (NF-κB) activation in the lungs of mice during sepsis. Honokiol also effectively rescued the lung edema, lung pathological changes, and lethality in septic mice. These findings suggest that Honokiol is capable of suppressing the lethal response and acute lung injury associated with sepsis, and support the potential use of Honokiol as a therapeutic agent for the conditions associated with septic shock.

  • inhibition of nadph oxidase related oxidative stress triggered signaling by Honokiol suppresses high glucose induced human endothelial cell apoptosis
    Free Radical Biology and Medicine, 2008
    Co-Authors: Meei Ling Sheu, Tei Weng, Chihkang Chiang, Kehsung Tsai, Shing-hwa Liu
    Abstract:

    Abstract Angiopathy is a major complication of diabetes. Abnormally high blood glucose is a crucial risk factor for endothelial cell damage. Nuclear factor-κB (NF-κB) has been demonstrated as a mediated signaling in hyperglycemia or oxidative stress-triggered apoptosis of endothelial cells. Here we explored the efficacy of Honokiol, a small molecular weight natural product, on NADPH oxidase-related oxidative stress-mediated NF-κB-regulated signaling and apoptosis in human umbilical vein endothelial cells (HUVECs) under hyperglycemic conditions. The methods of morphological Hoechst staining and annexin V/propidium iodide staining were used to detect apoptosis. Submicromolar concentrations of Honokiol suppressed the increases of NADPH oxidase activity, Rac-1 phosphorylation, p22phox protein expression, and reactive oxygen species production in high glucose (HG)-stimulated HUVECs. The degradation of IκBα and increase of NF-κB activity were inhibited by Honokiol in HG-treated HUVECs. Moreover, Honokiol (0.125–1 μM) also suppressed HG-induced cyclooxygenase (COX)-2 upregulation and prostaglandin E2 production in HUVECs. Honokiol could reduce increased caspase-3 activity and the subsequent apoptosis and cell death triggered by HG. These results imply that inhibition of NADPH oxidase-related oxidative stress by Honokiol suppresses the HG-induced NF-κB-regulated COX-2 upregulation, apoptosis, and cell death in HUVECs, which has the potential to be developed as a therapeutic agent to prevent hyperglycemia-induced endothelial damage.

Meei Ling Sheu - One of the best experts on this subject based on the ideXlab platform.

  • inhibition of nadph oxidase related oxidative stress triggered signaling by Honokiol suppresses high glucose induced human endothelial cell apoptosis
    Free Radical Biology and Medicine, 2008
    Co-Authors: Meei Ling Sheu, Tei Weng, Chihkang Chiang, Kehsung Tsai, Shing-hwa Liu
    Abstract:

    Abstract Angiopathy is a major complication of diabetes. Abnormally high blood glucose is a crucial risk factor for endothelial cell damage. Nuclear factor-κB (NF-κB) has been demonstrated as a mediated signaling in hyperglycemia or oxidative stress-triggered apoptosis of endothelial cells. Here we explored the efficacy of Honokiol, a small molecular weight natural product, on NADPH oxidase-related oxidative stress-mediated NF-κB-regulated signaling and apoptosis in human umbilical vein endothelial cells (HUVECs) under hyperglycemic conditions. The methods of morphological Hoechst staining and annexin V/propidium iodide staining were used to detect apoptosis. Submicromolar concentrations of Honokiol suppressed the increases of NADPH oxidase activity, Rac-1 phosphorylation, p22phox protein expression, and reactive oxygen species production in high glucose (HG)-stimulated HUVECs. The degradation of IκBα and increase of NF-κB activity were inhibited by Honokiol in HG-treated HUVECs. Moreover, Honokiol (0.125–1 μM) also suppressed HG-induced cyclooxygenase (COX)-2 upregulation and prostaglandin E2 production in HUVECs. Honokiol could reduce increased caspase-3 activity and the subsequent apoptosis and cell death triggered by HG. These results imply that inhibition of NADPH oxidase-related oxidative stress by Honokiol suppresses the HG-induced NF-κB-regulated COX-2 upregulation, apoptosis, and cell death in HUVECs, which has the potential to be developed as a therapeutic agent to prevent hyperglycemia-induced endothelial damage.

  • Honokiol induces calpain mediated glucose regulated protein 94 cleavage and apoptosis in human gastric cancer cells and reduces tumor growth
    PLOS ONE, 2007
    Co-Authors: Meei Ling Sheu, Shing-hwa Liu, Keng Hsin Lan
    Abstract:

    Background. Honokiol, a small molecular weight natural product, has been shown to possess potent anti-neoplastic and antiangiogenic properties. Its molecular mechanisms and the ability of anti-gastric cancer remain unknown. It has been shown that the anti-apoptotic function of the glucose-regulated proteins (GRPs) predicts that their induction in neoplastic cells can lead to cancer progression and drug resistance. We explored the effects of Honokiol on the regulation of GRPs and apoptosis in human gastric cancer cells and tumor growth. Methodology and Principal Findings. Treatment of various human gastric cancer cells with Honokiol led to the induction of GRP94 cleavage, but did not affect GRP78. Silencing of GRP94 by small interfering RNA (siRNA) could induce cell apoptosis. Treatment of cells with Honokiol or chemotherapeutics agent etoposide enhanced the increase in apoptosis and GRP94 degradation. The calpain activity and calpain-II (m-calpain) protein (but not calpain-I (mcalpain)) level could also be increased by Honokiol. Honokiol-induced GRP94 down-regulation and apoptosis in gastric cancer cells could be reversed by siRNA targeting calpain-II and calpain inhibitors. Furthermore, the results of immunofluorescence staining and immunoprecipitation revealed a specific interaction of GRP94 with calpain-II in cells following Honokiol treatment. We next observed that tumor GRP94 over-expression and tumor growth in BALB/c nude mice, which were inoculated with human gastric cancer cells MKN45, are markedly decreased by Honokiol treatment. Conclusions and Significance. These results provide the first evidence that Honokiol-induced calpain-II-mediated GRP94 cleavage causes human gastric cancer cell apoptosis. We further suggest that Honokiol may be a possible therapeutic agent to improve clinical outcome of gastric cancer. Citation: Sheu ML, Liu SH, Lan KH (2007) Honokiol Induces Calpain-Mediated Glucose-Regulated Protein-94 Cleavage and Apoptosis in Human Gastric Cancer Cells and Reduces Tumor Growth. PLoS ONE 2(10): e1096. doi:10.1371/journal.pone.0001096

  • Honokiol a small molecular weight natural product alleviates experimental mesangial proliferative glomerulonephritis
    Kidney International, 2006
    Co-Authors: Chihkang Chiang, Meei Ling Sheu, Kuanyu Hung, Shing-hwa Liu
    Abstract:

    Glomerulonephritis (GN) is still the most common cause of end-stage renal disease. Accumulation of glomerular macrophages, proliferation of mesangial cells, and deposition of extracellular matrix proteins are pathobiological hallmarks of GN. Pharmacological interventions that can inhibit these insults may be beneficial in the retardation of the progression of GN. Honokiol originally isolated from Magnolia officinalis , shows antioxidative, anti-inflammatory, and antiproliferative activities in a variety of inflammation models. In this study, we first investigated the in vivo effects of Honokiol on rat anti-Thy1 nephritis. Anti-Thy1 nephritis was induced in Wistar rats by injecting mouse anti-rat Thy1 antibodies intravenously. Nephritic rats were randomly assigned to receive Honokiol (2.5mg/kg, twice a day) or vehicle and were killed at various time points. Glomerular histology and immunohistopathology and urine protein excretion were studied. Western blotting was conducted for markers of proliferation. Adhesion molecules, chemokine, and extracellular matrix gene expression were evaluated by Northern blotting. Honokiol-treated nephritic rats excreted less urinary protein and had lower glomerular cellularity and sclerosis. The increased intraglomerular proliferating cell nuclear antigen and Akt phosphorylation in nephritic rats could be abolished by the treatment of Honokiol. Honokiol also alleviated glomerular monocyte chemoattractant protein-1 and intracellular adhesion molecule-1, similar to type I ( α 1) collagen and fibronectin mRNA levels of nephritic rats. These results indicate that Honokiol may have therapeutic potential in mesangial proliferative GN.

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

  • synergistic killing effect of paclitaxel and Honokiol in non small cell lung cancer cells through paraptosis induction
    Cellular Oncology, 2021
    Co-Authors: Jing Ren, Yi Wang, Yumin Zhu, Chenguo Chen, Weiguo Long, Qian Jiang
    Abstract:

    Purpose Paclitaxel is an anticancer drug for the treatment of non-small cell lung cancer (NSCLC). However, drug-resistance remains a major problem. Honokiol is a natural component which has been found to exhibit anti-tumor activity. Paclitaxel and Honokiol have been reported to be able to induce paraptosis. The aim of this study was to investigate whether Honokiol can reverse paclitaxel resistance by inducing paraptosis in NSCLC cells. Methods NSCLC cell lines H1650 (paclitaxel-sensitive), H1299 and H1650/PTX (intrinsic and acquired paclitaxel-resistant, respectively) were used to assess the cytotoxic effects of paclitaxel and Honokiol. Light and transmission electron microscopy were performed to detect cytoplasmic vacuolation. In vitro cell viability and clonogenic survival assays, as well as in vivo xenograft assays were conducted to test synergistic killing effects of paclitaxel and Honokiol on NSCLC cells. Western blotting, flow cytometry and immunofluorescence were performed to evaluate paraptosis-regulating mechanisms. Results We found that combination treatment with paclitaxel and Honokiol synergistically killed H1650, H1299 and H1650/PTX cells by inducing paraptosis, which is characterized by cytoplasmic vacuolation. Moreover, paclitaxel/Honokiol treatment resulted in a significant growth delay in H1299 xenograft tumors that showed extensive cytoplasmic vacuolation. Mechanistically, proteasomal inhibition-mediated endoplasmic reticulum (ER) stress and unfolded protein responses leading to ER dilation, and the disruption of intracellular Ca2+ homeostasis and mitochondrial Ca2+ overload resulting in mitochondrial disfunction, were found to be involved in paclitaxel/Honokiol-induced paraptosis. Cellular protein light chain 3 (LC3) may play an important role in paclitaxel/Honokiol induced cytoplasmic vacuolation and NSCLC cell death. Conclusions Combination of Honokiol and paclitaxel may represent a novel strategy for the treatment of paclitaxel-resistant NSCLC.

  • synergistic killing effect of paclitaxel and Honokiol in non small cell lung cancer cells through paraptosis induction
    Cellular Oncology, 2021
    Co-Authors: Jing Ren, Yi Wang, Yumin Zhu, Chenguo Chen, Weiguo Long, Qian Jiang
    Abstract:

    Paclitaxel is an anticancer drug for the treatment of non-small cell lung cancer (NSCLC). However, drug-resistance remains a major problem. Honokiol is a natural component which has been found to exhibit anti-tumor activity. Paclitaxel and Honokiol have been reported to be able to induce paraptosis. The aim of this study was to investigate whether Honokiol can reverse paclitaxel resistance by inducing paraptosis in NSCLC cells. NSCLC cell lines H1650 (paclitaxel-sensitive), H1299 and H1650/PTX (intrinsic and acquired paclitaxel-resistant, respectively) were used to assess the cytotoxic effects of paclitaxel and Honokiol. Light and transmission electron microscopy were performed to detect cytoplasmic vacuolation. In vitro cell viability and clonogenic survival assays, as well as in vivo xenograft assays were conducted to test synergistic killing effects of paclitaxel and Honokiol on NSCLC cells. Western blotting, flow cytometry and immunofluorescence were performed to evaluate paraptosis-regulating mechanisms. We found that combination treatment with paclitaxel and Honokiol synergistically killed H1650, H1299 and H1650/PTX cells by inducing paraptosis, which is characterized by cytoplasmic vacuolation. Moreover, paclitaxel/Honokiol treatment resulted in a significant growth delay in H1299 xenograft tumors that showed extensive cytoplasmic vacuolation. Mechanistically, proteasomal inhibition-mediated endoplasmic reticulum (ER) stress and unfolded protein responses leading to ER dilation, and the disruption of intracellular Ca2+ homeostasis and mitochondrial Ca2+ overload resulting in mitochondrial disfunction, were found to be involved in paclitaxel/Honokiol-induced paraptosis. Cellular protein light chain 3 (LC3) may play an important role in paclitaxel/Honokiol induced cytoplasmic vacuolation and NSCLC cell death. Combination of Honokiol and paclitaxel may represent a novel strategy for the treatment of paclitaxel-resistant NSCLC.

Shen Kou Tsai - One of the best experts on this subject based on the ideXlab platform.

  • Honokiol protects rat brain from focal cerebral ischemia reperfusion injury by inhibiting neutrophil infiltration and reactive oxygen species production
    Brain Research, 2003
    Co-Authors: Kuotong Liou, Yuhchiang Shen, Chiehfu Chen, Chengming Tsao, Shen Kou Tsai
    Abstract:

    Abstract We have previously shown that Honokiol, an active component of Magnolia officinalis, displayed protective effect against focal cerebral ischemia–reperfusion (FCI/R) injury in rats. Production of reactive oxygen species (ROS) and infiltration of neutrophils to injured tissue play deleterious roles during cerebral ischemia. To study the mechanism(s) in mediating neuroprotective effect of Honokiol, FCI/R-induced neutrophil infiltration and lipid peroxidation in brain tissue, and activation of neutrophils in-vitro were examined. Intravenous administration of Honokiol (0.01–1.0 μg/kg) 15 min before (pretreatment) or 60 min after (post-treatment) middle cerebral artery occlusion reduced the total infarcted volume by 20–70% in dose-dependent manner. Pretreatment or post-treatment of Honokiol at concentration of 0.1 and 1.0 μg/kg significantly decreased the neutrophil infiltration in the infarcted brain. Time course of neutrophil infiltration was performed in parallel with the lipid peroxidation in infracted brain tissue during FCI/R injury. The results indicate that Honokiol can protect brain tissue against lipid peroxidation and neutrophil infiltration during FCI/R injury and cerebral infarction induced by FCI/R is accompanied with a prominent neutrophil infiltration to the infarcted area during FCI/R course. In-vitro, Honokiol (0.1–10 μM) significantly diminished fMLP (N-formyl-methionyl-leucyl-phenylalanine)- or PMA (phorbol-12-myristate-13-acetate)-induced neutrophil firm adhesion, a prerequisite step behind neutrophil infiltration, and ROS production in neutrophils. Intracellular calcium overloading activates calcium-stimulated enzymes and further exaggerates FCI/R injury. Honokiol (0.1–10 μM) impeded the calcium influx induced by fMLP (a receptor agonist), AlF4− (a G-protein activator) or thapsigargin (an intracellular calcium pool releaser). Therefore, we conclude that the amelioration of FCI/R injury by Honokiol can be attributed to its anti-oxidative and anti-inflammatory actions through, at least in part, limiting lipid peroxidation and reducing neutrophil activation/infiltration by interfering firm adhesion, ROS production, and calcium overloading that may be primed/activated during FCI/R injury.

  • the anti inflammatory effect of Honokiol on neutrophils mechanisms in the inhibition of reactive oxygen species production
    European Journal of Pharmacology, 2003
    Co-Authors: Kuotong Liou, Shen Kou Tsai, Yuhchiang Shen, Chiehfu Chen, Chengming Tsao
    Abstract:

    Reactive oxygen species produced by neutrophils contribute to the pathogenesis of focal cerebral ischemia/reperfusion injury and signal the inflammatory response. We have previously shown that Honokiol, an active principle extracted from Magnolia officinalis, has a protective effect against focal cerebral ischemia/reperfusion injury in rats that paralleled a reduction in reactive oxygen species production by neutrophils. To elucidate the underlying mechanism(s) of the antioxidative effect of Honokiol, peripheral neutrophils isolated from rats were activated with phorbol-12-myristate-13-acetate (PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP) in the presence or absence of Honokiol. In this study, we found that Honokiol inhibited PMA- or fMLP-induced reactive oxygen species production by neutrophils by three distinct mechanisms: (1) Honokiol diminished the activity of assembled-NADPH oxidase, a major reactive oxygen species producing enzyme in neutrophils by 40% without interfering with its protein kinase C (PKC)-dependent assembly; (2) two other important enzymes for reactive oxygen species generation in neutrophils, i.e., myeloperoxidase and cyclooxygenase, were also inhibited by Honokiol by 20% and 70%, respectively; and (3) Honokiol enhanced glutathione (GSH) peroxidase activity by 30%, an enzyme that triggers the metabolism of hydrogen peroxide (H2O2). These data suggested that Honokiol, acting as a potent reactive oxygen species inhibitor/scavenger, could achieve its focal cerebral ischemia/reperfusion injury protective effect by modulating enzyme systems related to reactive oxygen species production or metabolism, including NADPH oxidase, myeloperoxidase, cyclooxygenase, and GSH peroxidase in neutrophils.

  • myocardial protective effect of Honokiol an active component in magnolia officinalis
    Planta Medica, 1996
    Co-Authors: Shen Kou Tsai, Shiang Suo Huang, Chuang Ye Hong
    Abstract:

    Honokiol is an active component of Magnolia officinalis. It was reported to be 1000 times more potent than alpha-tocopherol in inhibiting lipid peroxidation in rat heart mitochondria. In this study, we investigated the in vivo antiarrhythmic and antiischemic effects of Honokiol in coronary ligated rats. Male Sprague-Dawley rats were anesthetized with urethane. Honokiol, at dosages of 10(-7) g/kg, 10(-8) g/kg, and 10(-9) g/kg, was administered intravenously 15 min before ligation of the coronary artery. Incidence and duration of ventricular tachycardia and ventricular fibrillation during 30 min coronary ligation were significantly reduced by 10(-7) g/kg Honokiol. Ventricular arrhythmia during 10 min reperfusion after the relief of coronary ligation was also reduced. In rats subjected to 4 hours coronary ligation, 10(-7) g/kg, 10(-8) g/kg, and 10(-9) g/kg Honokiol significantly reduced the infarct zone. We concluded that Honokiol may protect the myocardium against ischemic injury and suppress ventricular arrhythmia during ischemia and reperfusion.