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

Jian Dai, Matthew A. Miller, Nicholas J. Everetts, Xia Wang, Peng Li, Ye Li, Jian Hua Xu, Guang Yao

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)13770-13781
Number of pages12
JournalOncotarget
Volume8
Issue number8
DOIs
StatePublished - 2017

Keywords

  • Cancer stem cells
  • Ganoderma lucidum
  • Natural compounds
  • Quiescence
  • Slow-cycling cells

ASJC Scopus subject areas

  • Oncology

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