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Reactive oxygen species‐mediated phosphorylation of p38 signaling is critically involved in apoptotic effect of Tanshinone I in colon cancer cells
Author(s) -
Kim Dong Hee,
Shin Eun Ah,
Kim Bonglee,
Shim Bum Sang,
Kim SungHoon
Publication year - 2018
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6126
Subject(s) - poly adp ribose polymerase , reactive oxygen species , p38 mitogen activated protein kinases , salvia miltiorrhiza , apoptosis , tunel assay , mapk/erk pathway , chemistry , cancer cell , microbiology and biotechnology , phosphorylation , viability assay , biology , biochemistry , cancer , medicine , enzyme , polymerase , pathology , genetics , alternative medicine , traditional chinese medicine
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.