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). CONCLUSION: 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.
OBJECTIVE: To investigate the growth inhibition and multidrug resistance (MDR) reversing effect of tanshinone I A on humanbreast cancer cells with estrogen receptor (ER) negative, and to elucidate its mechanism of activity. METHODS:HumanER 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). CONCLUSION: The findings in these studies suggest that tanshinone I A exhibits the potent cytotoxicity and MDR reversing potential to humanER 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.