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Author: search.filters.author.Tuchinda, PatoomratanaHas files: No

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    Suppression of PI3K/Akt/mTOR pathway in chrysoeriol-induced apoptosis of rat C6 glioma cells
    (2022-01-01)
    Wongkularb, Suppanut
    ;
    Limboonreung, Tanapol
    ;
    Tuchinda, Patoomratana
    ;
    Chongthammakun, Sukumal
    Chrysoeriol, a dietary methoxyflavonoid which is found in tropical medicinal plants, has been shown to have antioxidant, anti-inflammatory, and antineoplastic properties. The present study aimed to investigate the effects of chrysoeriol and its related mechanisms in rat C6 glioma cells. Cell viability in rat C6 glioma cells were measured by MTT assay. The protein expression levels of cleaved caspase-3, caspase-3, pro-apoptotic (Bax), anti-apoptotic protein (Bcl-2), and Annexin V were detected by Western blot analysis and immunocytochemical staining. Results showed that chrysoeriol significantly decreased cell viability and induced apoptosis in rat C6 glioma cells. Chrysoeriol significantly increased the levels of Bax/Bcl-2 ratio and cleaved caspase-3/caspase-3 ratio. Moreover, treatment with chrysoeriol significantly reduced the phosphorylation of PI3K, Akt, and mTOR expression in ratios. These results suggest that chrysoeriol promote apoptosis in rat C6 glioma cells via suppression of the PI3K/Akt/mTOR signaling pathway, thereby demonstrating the potential antineoplastic effects of chrysoeriol on glioma cells.
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    A novel potent autophagy inhibitor ECDD-S27 targets vacuolar ATPase and inhibits cancer cell survival
    (2019-12-01)
    Paha, Jiraporn
    ;
    Kanjanasirirat, Phongthon
    ;
    Munyoo, Bamroong
    ;
    Tuchinda, Patoomratana
    ;
    Suvannang, Naravut
    Autophagy is a conserved lysosomal-dependent cellular degradation process and its dysregulation has been linked to numerous diseases including neurodegeneration, infectious diseases, and cancer. Modulation of autophagy is therefore considered as an attractive target for disease intervention. We carried out a high-content image analysis screen of natural product-derived compounds to discover novel autophagy modulating molecules. Our screen identified ECDD-S27 as the most effective compound for increasing the number of autophagic vacuoles inside cells. The structure of ECDD-S27 revealed that it is a derivative of cleistanthin A, a natural arylnaphthalene lignan glycoside found in plants. ECDD-S27 increases the number of autophagic vacuoles by inhibiting the autophagic flux and is able to restrict the survival of different cancer cells at low nanomolar concentrations. Molecular docking and SERS analysis showed that ECDD-S27 may potentially target the V-ATPase. Upon treatment of various cancer cells with ECDD-S27, the V-ATPase activity is potently inhibited thereby resulting in the loss of lysosomal acidification. Taken together, these data indicated that ECDD-S27 retards the autophagy pathway by targeting the V-ATPase and inhibits cancer cell survival. The observed antitumor activity without cytotoxicity to normal cells suggests the therapeutic potential warranting further studies on lead optimization of the compound for cancer treatment.
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