Anti‐prostate cancer potential of gossypetin via inducing apoptotic and autophagic cell death

Lee, Ming-Shih; Tsai, Chia-Wen; Wang, Chi-Ping; Chen, Jing-Hsien; Lin, Hui-Hsuan

doi:10.1002/mc.22702

Cited by 16 publications

(15 citation statements)

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“…In addition, ROS have been demonstrated to activate autophagic death signaling pathway through AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) signaling pathway (20). Previous studies have demonstrated that many anticancer drugs can stimulate the production of ROS in cancer cells, and then lead to cell apoptosis and autophagic cell death (21,22).…”

Section: Introductionmentioning

confidence: 99%

α-hederin induces autophagic cell death in colorectal cancer cells through reactive oxygen species dependent AMPK/mTOR signaling pathway activation

et al. 2019

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α-hederin, a monodesmosidic triterpenoid saponin, had previously demonstrated strong anticancer effects. In the current study, the pharmacological mechanism of autophagic cell death induced by α-hederin was investigated in human colorectal cancer cells. First, through cell counting kit-8 and colony formation assays, it was demonstrated that α-hederin could inhibit the proliferation of HCT116 and HCT8 cell. Results of flow cytometry using fluorescein isothiocyanate Annexin V/propidium iodide and Hoechst 33258 staining indicated that α-hederin could induce apoptosis. Western blotting demonstrated that α-hederin could activate mitochondrial apoptosis signal pathway. Then, using light chain 3 lentiviral and electron microscope assay, it was demonstrated that α-hederin could induce autophagy in colorectal cancer cells. In addition, immunohistochemistry results from in vivo experiments also demonstrated that α-hederin could induce autophagy. AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) signaling was demonstrated to be activated by α-hederin, which could be blocked by reactive oxygen species (ROS) inhibitor NAC. Furthermore, NAC could inhibit apoptosis and autophagy induced by α-hederin. Finally, 3-MA (autophagy inhibitor) reduced the inhibition of α-hederin on cell activity, but it had no significant effect on apoptosis. In conclusion, α-hederin triggered apoptosis through ROS-activated mitochondrial signaling pathway and autophagic cell death through ROS dependent AMPK/mTOR signaling pathway activation in colorectal cancer cells.

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Section: Introductionmentioning

confidence: 99%

α-hederin induces autophagic cell death in colorectal cancer cells through reactive oxygen species dependent AMPK/mTOR signaling pathway activation

et al. 2019

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“…Annexin V-FITC detects the translocation of phosphatidylinositol from the inner to the outer cell membrane during early apoptosis, and 7-AAD can enter the cell in late apoptosis or necrosis [29]. After treatments, the cells were washed twice with cold PBS and resuspended in 1× binding buffer (BD Bioscience, Franklin Lakes, NJ, USA).…”

Section: Annexin V-fluorescein Isothiocyanate (Fitc) and 7-amino-actimentioning

confidence: 99%

“…Western blotting was performed as previously described [29,30]. In short, the cell lysates were denatured in a sample buffer containing sodium dodecyl sulfate (SDS), and equal amounts of total protein were separated on 8%-15% SDS-poly-acrylamide gels and transferred to nitrocellulose membranes.…”

Section: Western Blot Analysismentioning

confidence: 99%

Lotus Seedpod Extracts Reduced Lipid Accumulation and Lipotoxicity in Hepatocytes

et al. 2019

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Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic disorders, including hepatic lipid accumulation and lipotoxicity. Plant-derived polyphenols have attracted considerable attention in the prevention of NAFLD. Lotus seedpod, rich in polyphenols, is a traditional Chinese herbal medicine. Previous studies have showed that lotus seedpod possess radioprotective, antioxidant, anti-cancer, and anti-inflammatory activities. In this study, the in vitro hepatoprotective effect of lotus seedpod extract (LSE) and its main component epigallocatechin (EGC) was examined. Firstly, oleic acid (OA), an unsaturated fatty acid, was used to induce the phenotype of NAFLD in human hepatocytes, HepG2 cells. LSE dose-dependently improved the OA-induced viability loss of HepG2 cells. Non-cytotoxic concentrations of LSE or EGC abolished intracellular lipid accumulation and oxidative stress in the OA-treated cells. In addition, LSE and EGC showed a minor effect on autophagy, and potential in reducing OA-induced occurrence of apoptosis confirmed by morphological and biochemical features, including an increase in the formation of apoptotic bodies, the exposure of phosphatidylserine, and activation of caspases. Molecular data showed the anti-apoptotic effect of LSE might be mediated via downregulation of the mitochondrial pathway. Our data imply that EGC-enriched LSE potentially could be developed as an anti-NAFLD agent.

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“…Indeed, it has been reported that overactivation of AKT and PDK1 occurs in cancer cells [24][25][26], and antagonists of these kinases are regarded as anticancer drug candidates. Moreover, flavonoids have been shown to suppress tumor growth in a range of cancer types, including prostate cancer and pancreatic cancer, by targeting the PI3K/AKT and mTOR signaling pathways [27][28][29][30][31]. However, although mTOR has been shown to be downregulated by flavonoids as a result of direct interaction, the mechanism for inhibition of AKT by flavonoids remained unclear.…”

Section: Characterization Of the Inhibitory Effects Of Flavonoidsmentioning

confidence: 99%

Regulation of AKT Activity by Inhibition of the Pleckstrin Homology Domain-PtdIns(3,4,5)P3 Interaction Using Flavonoids

Kang

Jang

Ahn

et al. 2018

Journal of Microbiology and Biotechnology

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Since over‐activation of cellular signalling was frequently observed from a wide range of cancer types, the down‐regulation of signalling is regarded as a goal for drug development. A serine‐threonine kinase, AKT, playing a pivotal role in tumour progression was also over‐activated in cancer cells; thereby AKT was believed as a critical therapeutic target for cancer intervention. In this study, we targeted the pleckstrin homology (PH) domain to down‐regulate AKT activity via inhibiting phosphatidylinositol‐3,4,5‐triphosphate (PIP3) binding using by small natural molecules, flavonoids. The inhibition rates of flavonoids were evaluated by liposome pull‐down assay coupled with fluorescence spectrophotometry, and several flavonoids including 3,6‐dihydroxyflavone and 6,2′‐dihydroxyflavone showed about 40 and 50 % of inhibition at 10μM. Moreover, it was confirmed that flavonoids targeting PH domain‐PIP3 interaction decreased the activity of AKT in cellular levels. And then, we further analyzed the relationship between structure and activity using QSAR to find optimum structural moiety because of the structural similarity of flavonoids. Although it needed more study to derive optimum moiety of flavonoids as anticancer drugs for targeting AKT, we believed that this finding would provide a strong evidence to regulate AKT activity by targeting the regulatory domain instead of catalytic kinase domain. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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Anti‐prostate cancer potential of gossypetin via inducing apoptotic and autophagic cell death

Cited by 16 publications

References 50 publications

α-hederin induces autophagic cell death in colorectal cancer cells through reactive oxygen species dependent AMPK/mTOR signaling pathway activation

α-hederin induces autophagic cell death in colorectal cancer cells through reactive oxygen species dependent AMPK/mTOR signaling pathway activation

Lotus Seedpod Extracts Reduced Lipid Accumulation and Lipotoxicity in Hepatocytes

Regulation of AKT Activity by Inhibition of the Pleckstrin Homology Domain-PtdIns(3,4,5)P3 Interaction Using Flavonoids

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