Potential anticancer activity of tanshinone IIA against human breast cancer.
Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Danshen, a widely used Chinese herbal medicine. It has antioxidant properties and cytotoxic activity against multiple human cancer cell lines, inducing apoptosis and differentiation of some human cancer cell lines. Our purpose was to confirm its anticancer activity on human breast cancer in vitro and in vivo and to elucidate the mechanism of its activity. Human breast cancer cells were tested in vitro for cytotoxicity, colony formation inhibition, BrdU incorporation and gene expression profiling after treatment with tanshinone IIA. Seven nude mice bearing human breast infiltrating duct carcinoma orthotopically were tested for anticancer activity and expression of caspase-3 in vivo by s.c. injection of tanshinone IIA at a dose of 30 mg/kg 3 times/week for 10 weeks. Tanshinone IIA demonstrated a dose- and time-dependent inhibitory effect on cell growth (IC50 = 0.25 microg/ml), and it significantly inhibited colony formation and BrdU incorporation of human breast cancer cells. Oligonucleotide microarray analysis identified 41 upregulated (1.22%) and 24 downregulated (0.71%) genes after tanshinone IIA treatment. Upregulated genes were involved predominantly in cycle regulation, cell proliferation, apoptosis, signal transduction and transcriptional regulation; and downregulated genes were associated mainly with apoptosis and extracellular matrix/adhesion molecules. A 44.91% tumor mass volume reduction and significant increase of casepase-3 protein expression were observed in vivo. Our findings suggest that tanshinone IIA might have potential anticancer activity on both ER-positive and -negative breast cancers, which could be attributed in part to its inhibition of proliferation and apoptosis induction of cancer cells through upregulation and downregulation of multiple genes involved in cell cycle regulation, cell proliferation, apoptosis, signal transduction, transcriptional regulation, angiogenesis, invasive potential and metastatic potential of cancer cells. ADPRTL1 might be the main target at which tanshinone IIA acted.
Wang
Xiujie
X
Key Laboratory of Biotherapy of Human Diseases, Ministry of Education, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People's Republic of China. xiujiewang@sina.com
Wei
Yuquan
Y
Yuan
Shulan
S
Liu
Guanjian
G
Lu
Yanrong
Y
Zhang
Jie
J
Wang
Wendong
W
D045784:Abietanes; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D010616:Phenanthrenes / Q000494:pharmacology*; D014183:Transplantation, Heterologous
D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D010616:Phenanthrenes; C021751:tanshinone; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases