Combination of low-concentration of novel phytoestrogen (8,9)-furanyl-pterocarpan-3-ol from Pachyrhizus erosus attenuated tamoxifen-associated growth inhibition on breast cancer T47D cells
Objective: To investigate the estrogenic effect of (8,9)-furanyl-pterocarpan-3-ol (FPC) on growth of human breast cancer T47D cells and the interactions between the FPC and tamoxifen (TAM), on the growth of estrogen receptor-dependent breast cancer T47D cells. Methods: The proliferation effect of FPC were conducted on T47D cells in vitro by MTT test. T47D cells were treated with FPC alone (0.01-200 μmol/L) or in combination with TAM 20 nmol/L. Furthermore, the expression of ERα or c-Myc were also determined by immunohistochemistry. Results: The results indicated that administration of an anti-estrogen TAM showed growth inhibitory effect on T47D cells, wheraes co-administered with low concentration (less than 1 μmol/L) of FPC attenuated to promote cell proliferation. In contrast, the combination of TAM with higher doses (more than 20 μmol/L) of FPC showed growth inhibitory. This result was supported by immunocytochemistry studies that the administration of 20 nmol/L TAM down-regulated ER-α and c-Myc, but the combination of 20 nmol/L TAM and 1 μmol/L FPC robustly up-regulated expression of ER-α. Thus, the reduced growth inhibition of TAM 20 nmol/L by FPC 1 μmol/L on T47D cells may act via the modulation of ER-α. Conclusions: The findings indicate and suggest that FPC had estrogenic activity at low concentrations and anti-estrogenic effect that are likely to be regulated by c-Myc and estrogen receptors. We also confirm that low concentration of FPC attenuated the growth-inhibitory effects of TAM on mammary tumor prevention. Therefore, the present study suggests that caution is warranted regarding the consumption of dietary FPC by breast cancer patients while on TMA therapy.
Supported in part by Hibah Competition Grant Research of Faculty of Pharmacy, Gadjah Mada University (Grant No.UGM/FA/851.d/M/05/01).