Toremifene, a novel antiestrogen, can overcome hsp27-induced drug resistance in human breast cancer cells.

Human breast cancer cell lines derived from MDA-MB-231 were constructed to express hsp27 constitutively. The elevated presence of this protein resulted in an enhanced ability to survive a heat shock and exposure to doxorubicin, a chemotherapeutic agent. Hsp27 expression was unable to protect cells from doxorubicin if they were cultured in the presence of toremifene. Flow cytometry analysis indicated that wells exposed to both toremifene and doxorubicin accumulate at G2 + M. Protective effects of hsp27 were overcome by addition of an estrogen antagonist at clinically nontoxic levels. Addition of toremifene to chemotherapeutic regimes may enhance the sensitivity of breast cancer cells to doxorubicin.