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- Title
Discovery of Hesperidin Based Novel AMPK/mTOR Kinase Inhibitor against Colorectal Cancer Cells.
- Authors
Kumar, Vikas; Chauhan, Deeksha
- Abstract
Background/Aims Patient with inflammatory bowel disease are at high risk for expanding the colorectal cancer. Angiogenesis play an important and fundamental role in the expansion of solid tumor growth and development of chronic inflammation. Various mediators such as proliferation, angiogenesis, and expansion of tumor cells constantly expand the malignancy reactions. Metastasis and postoperative recurrences are still considering the major reason for breast cancer. Amusingly, like AMPK, mTOR serine/threonine kinase plays a significant role not only in cell proliferation and growth control but also in metabolism. AMPK/mTOR kinase is the major site for estimated the therapeutic effect because it validated important pathway. In the current experimental study, we showed that hesperidin exerted cytotoxic, pro-apoptotic and anti-proliferative effect against colorectal cancer cells via AMPK/mTOR signaling pathway. Methods Docking study was used for the estimated the effect of hesperidin on AMPK/mTOR signaling pathway. For, molecular and cellular mechanism, we performed the MTT assay and flow cytometirc on cell lines HT-29 and HCT-116 and scrutinized the possible mechanism against the collateral cancer via transforming growth factor beta (TGF-β) and AMPK/mTOR signaling pathway. Results Cell toxic experiments were able to predict inhibition with average of IC50 58.45 μmol/L. Hesperidin reduce the number of cell in S and G2-M phase and increase the cells in G0-G1 phase. Hesperidin induces the tumor cell apoptosis via concentration dependent manner. Hesperidin significantly reduced the invasion and migration of TGF-β induced HT-29 cells and HCT-116 in vitro. These effects were accompanied via reduced the MMP-2/9 protein expression and regulating the AMPK/mTOR signaling pathway via hesperidin, which suggest the role in coordinating anti-tumor metastasis. On docking study, we observed that hesperidin inhibit the AMPK/mTOR signaling pathway. Conclusions Overall, we can say that hesperidin could be safe agent for the prevention and treatment of colorectal cancer via AMPK/mTOR signaling pathway.
- Publication
Gut & Liver, 2019, Vol 13, Issue 6(suppl. 1), p35
- ISSN
1976-2283
- Publication type
Academic Journal