Faculty Publications
Potential of L-buthionine sulfoximine to enhance the apoptotic action of estradiol to reverse acquired antihormonal resistance in metastatic breast cancer
Potential of L-buthionine sulfoximine to enhance the apoptotic action of estradiol to reverse acquired antihormonal resistance in metastatic breast cancer
J Steroid Biochem Mol Biol. 2009 Mar;114(1-2):33-9.
Abstract L-Buthionine sulfoximine (BSO) is a potent inhibitor of glutathione biosynthesis and studies have shown that it is capable of enhancing the apoptotic effects of several chemotherapeutic agents. Previous studies have shown that long-term antihormonal therapy leads to acquired drug resistance and that estrogen, which is normally a survival signal, is a potent apoptotic agent in these resistant cells. Interestingly, we have developed an antihormone-resistant breast cancer cell line, MCF-7:2A. which is resistant to estrogen-induced apoptosis but has elevated levels of glutathione. In the present study, we examined whether BSO is capable of sensitizing anti hormone-resistant MCF-7:2A cells to estrogen-induced apoptosis. Our results showed that treatment of MCF-7:2A cells with 1 nM E2 plus 100 mu M BSO combination for 1 week reduced the growth of these cells by almost 80-90% whereas the individual treatments had no significant effect on growth. TUNEL and 4',6-diamidino-2-phenylindole (DAPI) staining showed that the inhibitory effect of the combination treatment was due to apoptosis. Our data indicates that glutathione participates in retarding apoptosis in antihormone-resistant human breast cancer cells and that depletion of this molecule by BSO may be critical in predisposing resistant cells to estrogen-induced apoptosis. (C) 2009 Published by Elsevier Ltd.