Tanshinone I effectively induces apoptosis in estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) breast cancer cells.
Danshen (Salvia miltiorrhiza Bunge) is a herb that has been widely and successfully used for treating inflammatory diseases in clinics in Asia. The relatively abundant tanshinones, tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone, have been isolated from Danshen. These tanshinones are the major diterpenes isolated from Danshen, and show cytotoxic effects on cell lines derived from human carcinomas of the colon, ovary, lung, mouth, and breast. Recently, anti-cancer activities of tanshinone IIA have been reported, which suggest that the structurally similar tanshinone I may possess similar cytotoxic effects on tumor cells. We investigated the effect of tanshinone I on the induction of apoptosis in human breast cancer cells (MCF-7 and MDA-MB-231) in vitro. Tanshinone I inhibited cell proliferation of MCF-7 and MDA-MB-231 cells in a dose- and time-dependent manner, as assayed by MTT. In addition, TUNEL assay and flow cytometry showed that tanshinone I significantly induced apoptosis in MCF-7 and MDA-MB-231 cells. The induction of apoptotic cell death was mediated by the activation of caspase 3, the downregulation of the level of the anti-apoptotic protein, Bcl-2, and the upregulation of the level of the pro-apoptotic protein, Bax. Taken together, these results reveal a potential mechanism for the anti-cancer effect of tanshinone I on human breast cancer cells, and suggest that tanshinone I may serve as an effective adjunctive reagent in the treatment of human breast cancer.
Nizamutdinova
Irina Tsoy
IT
Department of Pharmacology, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju, South Korea.
Lee
Gyeong Won
GW
Son
Kun Ho
KH
Jeon
Su Jin
SJ
Kang
Sam Sik
SS
Kim
Yeong Shik
YS
Lee
Jae Heun
JH
Seo
Han Geuk
HG
Chang
Ki Churl
KC
Kim
Hye Jung
HJ
D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D010616:Phenanthrenes / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000187:drug effects; D011960:Receptors, Estrogen / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000187:drug effects
D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D010616:Phenanthrenes; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D051028:bcl-2-Associated X Protein; C021751:tanshinone; D053148:Caspase 3