Suppression of cell proliferation and regulation of estrogen receptor alpha signaling pathway by arsenic trioxide on human breast cancer MCF-7 cells.
In recent years, breast cancers have aroused much concern. Together with a growing incidence all over the world, the development of drug resistance to tamoxifen, the most commonly prescribed chemotherapeutic drug for breast cancer patients, has highlighted the importance of developing a new chemotherapeutic drug in combating breast cancer. With the aim of treating breast cancers, the anti-tumor effects of arsenic trioxide in MCF-7 cells have been studied. MCF-7 cells are estrogen responsive cells which mimic breast cancers at the early stage. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and direct cell counting were used to measure cell proliferation. The mechanisms of action were elucidated through the measurement of estrogen receptor (ER) binding, mRNA and protein levels of ERalpha and its activity. We have demonstrated that arsenic trioxide was capable of reducing cell survival in MCF-7 cells via the suppression of the estrogen-induced growth stimulatory effects in MCF-7 cells. Arsenic trioxide was shown to suppress the action of estrogen through the regulation of the ERalpha signaling pathway. Arsenic trioxide could down-regulate ERalpha mRNA and protein levels without competing with estrogen for ERalpha binding. Arsenic trioxide also inhibited the transcription activity mediated by the ERalpha signaling pathway and ultimately it down-regulated c-myc protein expression and inhibited cell entry to S phase under estrogen's stimulation. In conclusion, arsenic trioxide could inhibit the growth of MCF-7 cells by reducing the growth stimulatory effect of estrogen. As estrogen is a primary risk factor in promoting the growth of breast tumor cells, the anti-estrogenicity exhibited by arsenic trioxide sheds light on the therapy of breast cancer.
Department of Biochemistry, Mong Man Wai Building, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Stephanie K Y
SK
Chow
Judy Y W
JY
Chan
Kwok Pui
KP
Fung
D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use*; D047628:Estrogen Receptor alpha; D005260:Female; D006801:Humans; D010087:Oxides / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D001152:Arsenicals; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D010087:Oxides; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D000077237:Arsenic Trioxide