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.
Highlights
Ganoderma lucidum, famously known in Asian countries as Lingzhi or Reishi, is a mushroom species used in traditional Chinese medicine for disease treatment and longevity promotion for more than 2,000 years
We studied the cytotoxic effects of two natural compounds purified from Ganoderma lucidum, ergosterol peroxide and ganodermanondiol
With MCF7 breast cancer epithelial cells, cytotoxicity was seen at higher compound doses and longer treatment durations: LC50s were estimated at 20 μg/ml with ergosterol peroxide and ganodermanondiol treatment for about 2 and 2.6 days, respectively (Figure 1B)
Summary
Famously known in Asian countries as Lingzhi or Reishi, is a mushroom species used in traditional Chinese medicine for disease treatment and longevity promotion for more than 2,000 years. It has been widely reported that the active components of Ganoderma lucidum exhibit therapeutic antitumor, antiviral, antiinflammatory and immunomodulatory effects, and are beneficial to treatment of diseases including cancer, AIDS, hypertension, hepatitis, and diabetes [4,5,6,7,8]. The antitumor effects of Ganoderma lucidum have been linked to cell cycle arrest, induction of cytotoxicity and apoptosis, induction of differentiation, suppression of angiogenesis and cell migration, and immunomodulation [9,10,11,12]. These documented effects primarily regard proliferating cancer cells. Little is known about the effects of Ganoderma lucidum against the quiescent, slow-cycling subpopulation of cancer cells (including but not limited to cancer stem cells), which often leads to cancer recurrence [13, 14]
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