Elimination of quiescent slow-cycling cells via reducing quiescence depth by natural compounds purified from Ganoderma lucidum

The medical mushroom Ganoderma lucidum has long been used in traditional Chinese medicine and shown effective in the treatment of many diseases including cancer. Here we studied the cytotoxic effects of two natural compounds purified from Ganoderma lucidum, ergosterol peroxide and ganodermanondiol. We found that these two compounds exhibited cytotoxicity not only against fast proliferating cells, but on quiescent, slow-cycling cells. Using a fibroblast cell-quiescence model, we found that the cytotoxicity on quiescent cells was due to induced apoptosis, and was associated with a shallower quiescent state in compound-treated cells, resultant from the increased basal activity of an Rb-E2F bistable switch that controls quiescence exit. Accordingly, we showed that quiescent breast cancer cells (MCF7), compared to its non-transformed counterpart (MCF10A), were preferentially killed by ergosterol peroxide and ganodermanondiol treatment presumably due to their already less stable quiescent state. The cytotoxic effect of natural Ganoderma lucidum compounds against quiescent cells, preferentially on quiescent cancer cells vs. non-cancer cells, may help future antitumor development against the slow-cycling cancer cell subpopulations including cancer stem and progenitor cells.This work was supported by grants from the Program of International S&T Cooperation (2013DFA30900, to J-H.X., Y.L., and G.Y.) of the Ministry of Sci. & Tech. of China, the Joint Funds for the Innovation of Science and Technology, Fujian province, China (2016Y9059, to J-H.X.), and the National Science Foundation of the USA (DMS1463137 and DMS1418172, to G.Y.).Open access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu