Tanshinone IIA inhibits BT-20 human breast cancer cell proliferation             through increasing caspase 12, GADD153 and phospho-p38 protein expression.
Breast cancer is the leading cause of cancer-related deaths in women worldwide.             Tanshinone IIA (Tan-IIA) is one of the pure compounds from Salviae miltiorrhizae             radix (Danshen). Tan-IIA can inhibit human breast cancer cells but the molecular             mechanisms are not well understood. Our previous study showed that Tan-IIA can             inhibit hep-J5 human hepatocellular carcinoma cells through the endoplasmic reticulum             (ER) stress-induced apoptotic pathway. In the present study, we evaluated the             effects of Tan-IIA on BT-20 human breast cancer cells and assessed the involvement             of the ER-stress-apoptotic pathway. The cytotoxicity of Tan-IIA in BT-20 cells             was measured by the MTT assay. The cell cycles were analyzed by flow cytometry.             The expression of ER stress-related proteins in BT-20 cells treated with Tan-IIA             were evaluated by western blotting and immunocytochemical staining. These results             showed that Tan-IIA can inhibit BT-20 cells and increase the sub-G1 phase in a             time- and dose-dependent manner. Tan-IIA could increase the protein expression             of caspase 12, GADD153, caspase 3, phospho-JNK, phospho-p38 and Bax, but decreased             Bcl-xl and phospho-ERK expression in BT-20 cells. These findings indicate that             Tan-IIA possesses therapeutic potential for human breast cancer BT-20 cells; one             of the molecular mechanisms may be through inducing ER stress and the MAPK pathway             to induce apoptosis and inhibit proliferation.
Department of Surgery, Changhua Christian Hospital, Changhua, Changhua County 50006, Taiwan, R.O.C.
Meng-Yi
MY
Yan
Su-Yu
SY
Chien
Shou-Jen
SJ
Kuo
Dar-Ren
DR
Chen
Chin-Cheng
CC
Su
D045784:Abietanes / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D053454:Caspase 12 / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D051742:Transcription Factor CHOP / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics
D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; C021751:tanshinone; D051742:Transcription Factor CHOP; D048051:p38 Mitogen-Activated Protein Kinases; D053454:Caspase 12