Research Papers:

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 and Guang Yao _

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Oncotarget. 2017; 8:13770-13781. https://doi.org/10.18632/oncotarget.14634

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Jian Dai1,4, Matthew A. Miller1, Nicholas J. Everetts1, Xia Wang1, Peng Li2, Ye Li3, Jian-Hua Xu2, Guang Yao1,5

1Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, USA

2School of Pharmacy and Fujian Key Laboratory of Natural Medicine Pharmacology, Fujian Medical University, Fuzhou, Fujian, China

3Fujian Xianzhilou Biological Science and Technology Co, Ltd, Fuzhou, Fujian, China

4Jiangsu Academy of Agricultural sciences, Nanjing, Jiangsu, China

5Arizona Cancer Center, University of Arizona, Tucson, AZ, USA

Correspondence to:

Guang Yao, email: [email protected]

Jian-Hua Xu, email: [email protected]

Ye Li, email: [email protected]

Keywords: quiescence, natural compounds, ganoderma lucidum, slow-cycling cells, cancer stem cells

Received: May 01, 2016     Accepted: January 03, 2017     Published: January 13, 2017


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.

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