Investigating synergistic effects of ganoderma lucidum extracts in combination with tamoxifen and doxorubicin in breast cancer cell lines.

Ganoderma lucidum, an edible medicinal fungus, has been known with its anti-metastatic, anti-carcinogenic bioactivities and widely used in Asian countries in complementary and alternative medicine. However, there is no information regarding its combined usage with tamoxifen and doxorubicin in breast cancer treatment. In this study, effects on cell viability of six distinct extracts obtained from G.lucidum were assessed by WST-8 method in MCF-7 estrogen receptor positive and MDA-MB-231 triple negative breast cancer cell lines. Ganoderma lucidum ether extract was the most effective extract on inhibition of cell viability among others in both cell lines. Ether extract was then evaluated in terms of its anti-metastatic activity using Boyden Chamber Assay. Ether extract significantly decreased the number of migrated cells in MDA-MB-231; however did not affect MCF-7 mobility. There was no difference in invaded cell number between DMSO and ether extract treated cells in both cell lines. Apoptosis and cell cycle analysis were performed by flow cytometry. We found that ether extract is capable of inducing apoptosis in MCF-7 and MDA-MB-231 cells. Additionally, incubation with ether extract significantly changed the cell cyle dynamics in both cell lines. We then assessed the interactions between ether extract and tamoxifen citrate and/or doxorubicin in breast cancer cell lines. The interactions between G. lucidum ether extract and chemotherapeutics were examined by combination index analysis and MacSynergy II software. Ether extract increased the anti-proliferative effect of tamoxifen although exhibited strong antagonism with doxorubicin in MCF-7 cell line. Ether extract also showed antagonistic effect with doxorubicin in MDA-MB-231 triple negative breast cancer cell line.