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Twenty-one xanthone derivatives (XDs) were synthesized by a microwave-assisted technique. Their inhibition potency against the growth of four cancer cell lines was evaluated. XD-1 ∼ [6,9,10-trihydroxy-3,3-dimethyl-5-(2-methylbut-3-en-2-yl)-3,7-pyrano[2,3-]xanthen-7-one] was confirmed as the most active agent against HepG2 cell line growth with IC of 18.6 ± 2.31 μM. Apoptosis analysis indicated different contributions of early/late apoptosis and necrosis to cell death for XD-1. XD-1 arrested HepG2 cells on the G0/G1 phase, as indicated by the decreased expressions of cyclin D and CDK2 and the increased expressions of p21. Western blot implied that XD-1 regulated p53/MDM2 to a better healthier state. Moreover, XD-1-induced cell apoptosis was mitochondrion-mediated, as evidenced by caspase activation and involved the PI3K/AKT/mTOR signaling pathway. All the evidence supports that XD-1 is a significant anti-cancer agent for HCC.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9076231PMC
http://dx.doi.org/10.1039/c9ra06408gDOI Listing

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