Yuehchukene, a bis-indole alkaloid, and cyclophosphamide are active in breast cancer in vitro

Yuehchukene (YCK) is a novel bis-indole alkaloid with weak estrogenic activity. Biochemical studies showed that YCK could attenuate estrogenic action. In this study, the response of MCF-7, an estrogen-receptor-positive breast cancer cell line, under different combinations of estradiol, cyclophosphamide and YCK, was tested. From the dose-response curve, we discovered that 10-2M cyclophosphamide, even in its so-called 'bio-inert' form, could inhibit MCF-7 cell growth. However, the cytotoxic effect of cyclophosphamide was lost by reducing its concentration to ~ 1 x 10-3M. On the other hand, a low concentration (~ 10-8-10-9M) of YCK was found to potentiate the cytotoxic effect of cyclophosphamide on the MCF-7 cell line. Such an effect was absent in the estrogen-receptor-negative cell line MDA-MB-231. These findings, together with the dual role of a mixed estrogen and anti-estrogen effect, suggested that YCK and cyclophosphamide can be a potential combination in chemo-hormonal therapy for breast cancer.