[Growth inhibition and multidrug resistance-reversing effect of tanshinone I A on human breast cancer cell with estrogen receptor negative].
OBJECTIVE
To investigate the growth inhibition and multidrug resistance (MDR) reversing effect of tanshinone I A on human breast cancer cells with estrogen receptor (ER) negative, and to elucidate its mechanism of activity.


METHODS
Human ER negative breast cancer cells (MDA-MB-231) were tested in vitro for cytotoxicity and colony formation inhibition. Brdu incorporation and cell cycle distribution were also checked through flow cytometry (FCM). With RT-PCR, the expressions of ADP-ribosyltransferase CNAD+; poly (ADP-ribose) polymerase)-like 1 (ADPRTL1), cytochrome P450 subfamily I (CYP1A1) and breast cancer resistance protein (BCRP/ABCG2) mRNA were detected for testing the response to tanshinone 1 A treatment.


RESULTS
After tanshinone I A treatment, the proliferation, colony formation and Brdu labeling indices of cancer cells decreased (P<0. 05). By FCM analysis, the increase of subG, and G0/G1 phase cell populations and decrease of S and G2/M phase cells were observed (P<O. 01), both ADPRTL1 and CYP1A1 mRNA expression increased (P< 0. 05), while BCRP/ABCG2 mRNA expression was decreasing (P<0. 05).


CONCLUSIONS
The findings in these studies suggest that tanshinone I A exhibits the potent cytotoxicity and MDR reversing potential to human ER negative breast cancer cells. The mechanism for such effects may be associated with the inhibition of DNA synthesis, induction of apoptosis, cell cycle arrest and up-regulation of ADPRTL1, CYP1A1, and down-regulation of BCRP/ABCG2 expression in cancer cells.
Jing
Jing
J
Experimental Oncology Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
Zheng
Hong
H
Wang
Jing
J
Lin
Ping
P
Zhang
Jie
J
Xiong
Zhu-juan
ZJ
Wu
Ya-ying
YY
Ren
Jing-jing
JJ
Yang
Hong-liang
HL
Wang
Xiu-jie
XJ
D045784:Abietanes; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D010616:Phenanthrenes / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000378:metabolism*
D045784:Abietanes; D000970:Antineoplastic Agents; D010616:Phenanthrenes; D011960:Receptors, Estrogen; C021751:tanshinone; D001973:Bromodeoxyuridine