Regulation of cell cycle transition and induction of apoptosis in HL-60 leukemia cells by the combination of Coriolus versicolor and Ganoderma lucidum

Abstract

Medicinal mushrooms have served as the mainstay of treatment for a variety of human illnesses in Asian countries, mostly as supplements by cancer patients. Extracts prepared from Trametes versicolor under the trade name of I'm-Yunity exhibit anti-tumorigenic activities, as supported by inhibition of the proliferation and induction of apoptosis in malignant cells. Similar effects have also been observed for the Reishi mushroom Ganoderma lucidum. The two mushrooms exert their medicinal activities primarily through a family of polysaccharo-peptides. Despite the common identity in their bioactive ingredients, whether their combination might elicit an expanded efficacy and mechanism has not been investigated. In the present study, we investigated similarities and differences between extracts prepared from I'm-Yunity and from a formulation denoted I'm-Yunity-Too combining I'm-Yunity and Ganoderma lucidum. By assaying their anti-proliferative and anti-apoptotic effects using human promyelocytic HL-60 cells, we found that the ethanolic extract of I'm-Yunity-Too was more active in inducing cell death compared to I'm-Yunity, based on measured changes in the expression of caspase 3 and Bax. Moreover, ethanolic extracts of I'm-Yunity-Too exhibited more potent activity compared to its aqueous extracts with regard to suppression of the growth and induction of apoptosis, as assayed by the more pronounced downregulation of phosphorylation of Rb and increased cleavage of poly(ADP-ribose) polymerase (PARP) from its native 112-kDa form to the inactive 89-kDa product. These results suggested that the chemopreventive potential of I'm-Yunity may be enhanced by adding Ganoderma lucidum and that their bioactive ingredients potentially exhibit mechanistic synergism suggesting a more efficacious adjunct in chemotherapy.