Growth inhibition and apoptosis induction by tanshinone IIA in human colon adenocarcinoma cells.
Tanshinone IIA is the most abundant diterpene quinone in Danshen, Salviae miltiorrhizae Radix, a widely prescribed traditional herbal medicine that is used to treat cardiovascular and inflammatory diseases. Recently, tanshinone IIA was demonstrated to induce cell death and apoptosis in a variety of tumors. However, the effect of tanshinone IIA on human colon cancer cells is not clearly understood yet. In this study, the antigrowth and apoptosis-eliciting effects of tanshinone IIA, as well as its cellular mechanisms of actions, were investigated in Colo-205 human colon cancer cells. Tanshinone IIA reduced cell growth in a concentration-dependent manner, inducing apoptosis accompanied by an increase in TUNEL staining and by an increased percentage of cells in the sub-G1 fraction. The expression of p53 and p21 and mitochondrial cytochrome c release were increased in tanshinone IIA-treated cells. In addition, the expression of Fas proteins was up-regulated by tanshinone IIA. Tanshinone IIA-induced catalytic activation of caspases was confirmed by cleavage of caspase-8 and caspase-3. These findings suggest that tanshinone IIA induces apoptosis in Colo-205 cells through both mitochondrial-mediated intrinsic and Fas-mediated extrinsic caspase cell-death pathways. Accordingly, the chemotherapeutic potential of tanshinone IIA for colon cancer warrants further study.
Su
Chin-Cheng
CC
Division of General Surgery, Department of Surgery, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan.
Chen
Guang-Wei
GW
Kang
Jung-Cheng
JC
Chan
Ming-Huan
MH
D045784:Abietanes; D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D041702:BALB 3T3 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy; D006801:Humans; D051379:Mice; D010616:Phenanthrenes / Q000494:pharmacology* / Q000627:therapeutic use
D045784:Abietanes; D010616:Phenanthrenes; C021751:tanshinone