Tanshinone IIA down-regulates the protein expression of ErbB-2 and up-regulates TNF-alpha in colon cancer cells in vitro and in vivo.
Tanshinone IIA (Tan-IIA) was isolated from Salviae Miltiorrhizae Radix. Our previous studies showed that Tan-IIA induced apoptosis in human colon cancer colo 205 cells, but the molecular mechanisms of the effect of Tan-IIA on human colon cancer were not clearly elucidated. The protein expression of ErbB-2 was up-regulated and activated in human and experimental colon cancers. In the present study, the effects of Tan-IIA on the protein expression of ErbB-2 in colo 205 cells were investigated. In vitro, colo 205 cells were treated with various concentrations of Tan-IIA (1, 2 and 5 mug/ ml) for 24 h, and the protein expression of TNF-alpha, ErbB-2 and caspase-3 was assayed by Western blotting. For the in vivo studies, male SCID mice were xenografted with colo 205 cells, and from day 10, Tan IIA (20 mg/kg/day, dissolved in corn oil) was administered by oral feeding for 30 days. As a control, mice with xenografted tumors were separately treated with corn oil (0.1 ml/10 g body weight). Expression of TNF-alpha, ErbB-2 and caspase-3 proteins was measured by Western blot analysis. Our results showed that Tan-IIA down-regulated the protein expression of ErbB-2 and up-regulated TNF-alpha and caspase-3 in colo 205 cells in vitro. In a colo 205 xenograft model, treatment with Tan-IIA caused up-regulation of TNF-alpha, caspase-3 and down-regulation of ErbB-2 protein expression as compared to the controls. Based on these observations, one possible molecular mechanisms by which Tan-IIA inhibits the proliferation of colo 205 cells is through the down-regulation of ErbB-2 protein expression and the up-regulation of the protein expression of TNF-alpha and caspase-3.
Su
Chin-Cheng
CC
Division of General Surgery, Buddhist Tzu Chi General Hospital, Hualien City 970, Taiwan. succ.maeva@msa.hinet.net
Lin
Yi-Hsiang
YH
D045784:Abietanes; D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010616:Phenanthrenes / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D045784:Abietanes; D000199:Actins; D000972:Antineoplastic Agents, Phytogenic; D053148:Caspase 3; D010616:Phenanthrenes; D018719:Erb-b2 Receptor Tyrosine Kinases; D014409:Tumor Necrosis Factor-alpha; C021751:tanshinone