Mechanisms of crude protein from medicinal mushroom Ophiocordyceps sobolifera against human breast MCF-7 cancer cells

Abstract

The mycelial extract of the entomopathogenic fungus Ophiocordyceps sobolifera has recently been reported to have anti-bacterial, anti-fungal and anti-cancer effects; however, there have been no reports on the medicinal value of the crude protein against the Michigan Cancer Foundation-7 (MCF-7) human breast cancer cell line. Therefore, in this study, crude proteins from 11 isolates of O. sobolifera were subjected to screening and evaluation for potential anticancer activity against a breast cancer cell line. The cytotoxic and antiproliferative effects of the crude proteins on human breast cancer MCF-7 cell line was investigated using the sulforhodamine B (SRB) assay and colony formation. The gene expression and cell cycle-associated protein levels were assayed by reverse transcription-quantitative polymerase chain reaction and western blotting analysis. The results showed that the crude proteins of all isolates had anti-cancer activity in a time- and dose-dependent manner. Among them, isolates Cod-KK1524, Cod-KK1630, Cod-KK1643 and Cod-KS1601 had greater inhibitory effects against cancer cells; therefore, these were chosen for further evaluation of anti-cancer mechanisms. These crude proteins exhibited a potent anticancer effect on the MCF-7 cells by inhibiting colony formation in a dose-dependent manner. Furthermore, the crude proteins significantly decreased the cyclin-dependent kinase 6 (cdk6) and cyclin D1 expression. Additionally, crude proteins significantly enhanced the potent cyclin-dependent kinase inhibitor (p21) levels, and reduced the expression level of the cell cycle protein, cyclin D1. These findings indicate that the crude protein of the entomopathogenic fungus O. sobolifera may be useful for developing an anti-cancer drug candidate for breast cancer therapeutic treatment.