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  • Title: Reactive oxygen species-mediated phosphorylation of p38 signaling is critically involved in apoptotic effect of Tanshinone I in colon cancer cells.
    Author: Kim DH, Shin EA, Kim B, Shim BS, Kim SH.
    Journal: Phytother Res; 2018 Oct; 32(10):1975-1982. PubMed ID: 29876988.
    Abstract:
    Though Tanshinone I (Tan I), a phenolic compound from Salvia miltiorrhiza, is known to have anticancer activity in several cancers, its anticancer mechanisms are not fully understood in colon cancer cells. Thus, in the present study, the underlying molecular mechanism of Tan I was explored in HCT116 and HT29 colorectal cancer cells (CRCs). Here, Tan I suppressed viability in HCT116 and HT29 cells in a time- and dose-dependent manner. Also, Tan I increased the number of terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL)-positive cells and sub-G1 population in HCT116 and HT29 cells. Consistently, Tan I cleaved poly (adenosine diphosphate-ribose) polymerase (PARP) and caspase-8, caspase-3, attenuated the expression of Bid and activated tBid as a caspase-8 substrate and activated phosphorylation of p38 MAPK in HCT116and HT29 cells. Of note, Tan I generated reactive oxygen species (ROS) and conversely an ROS scavenger, N-acetyl-L -cysteine, reversed ROS production, PARP cleavage, caspase-3 activation, and p38 MAPK phosphorylation induced by Tan I in HCT116 cells. Furthermore, p38 MAPK inhibitor SB203580 reduced cytotoxicity, increase of TUNEL-positive cells, cleavages of PARP and caspase-3 induced by Tan I in HCT116 cells. Overall, our findings for the first time suggest that ROS-dependent activation of p38 MAPK and caspase-3 is critically involved in Tan I induced apoptosis in CRCs as a potent anticancer agent.
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