16-Hydroxycleroda-3,13-dien-15,16-olide and N-Methyl-Actinodaphine Potentiate Tamoxifen-Induced Cell Death in Breast Cancer

In this study, we investigated whether 16-hydroxycleroda-3,13-dien-15,16-olide (HCD) and N-methyl-actinodaphine (MA) could sensitize breast cancer cells to Tamoxifen (TMX) treatment. MA or HCD alone or in combination with TMX dose-dependently inhibited MCF-7 and MDA-MB-231 cell growth, with a more potent inhibition on MDA-MB 231 cells. Furthermore, this novel combination significantly induced S and G2/M cell cycle phase in MDA-MB 231 than MCF-7 cells. Further determination of the apoptotic induction showed that MA or HCD and TMX combination inhibited MDA-MB-231 and MCF-7 cancer cells by upregulating Bax and by downregulating Bcl-2 mRNA and protein expression without altering Caspase-8 and Caspase-12 expression. These results suggest that MA or HCD pretreatment may potentiate the anti-tumor effect of tamoxifen on breast cancer.