Grifolin, a potential antitumor natural product from the mushroom Albatrellus confluens, inhibits tumor cell growth by inducing apoptosis in vitro

Abstract

Grifolin is a natural biologically active substance isolated from the fresh fruiting bodies of the mushroom Albatrellus confluens. Here, for the first time, we describe a novel activity of grifolin, namely its ability to inhibit the growth of tumor cells by the induction of apoptosis. Grifolin strongly inhibited the growth of tumor cell lines: CNE1, HeLa, MCF7, SW480, K562, Raji and B95-8. Analysis of acridine orange (AO)/ethidium bromide (EB) staining and flow cytometry showed that grifolin possessed apoptosis induction activity to CNE1, HeLa, MCF7 and SW480. Furthermore, the cytochrome c release from mitochondria was detected by confocal microscopy in CNE1 cells after a 12 h treatment with grifolin. The increase of caspase-8, 9, 3 activities revealed that caspase was a key mediator of the apoptotic pathway induced by grifolin, and the underexpression of Bcl-2 and up-regulation of Bax resulted in the increase of Bax: Bcl-2 ratio, suggesting that Bcl-2 family involved in the control of apoptosis. Owing to the combination of the significant antitumor activity by inducing apoptosis and natural abundance of the compound, grifolin holds the promise of being an interesting antitumor agent that deserves further laboratory and in vivo exploration.

Progress on Understanding the Anticancer Mechanisms of Medicinal Mushroom: Inonotus Obliquus

“…The activities of two types of cyclins (cyclin D and cyclin E), Cdks (cyclin-dependent kinases 2, 4 and 6), and Cdks inhibitors are necessary for entering from the G1 phase into S phase of the cell cycle (Weinberg, 1989). Thus, most of bioactive substances from natural products have been reported to exert their anticancer activity by blocking cell cycle progression and triggering tumor cell apoptosis (Chang et al, 2004;Ye et al, 2005;Hsieh et al, 2006). Youn et al (2008) confirmed that I. obliquus water extract (IWE) previously used for treating cancers and digestive system diseases could selectively and significantly inhibited the viability and proliferation, and induced apoptotic cell death in human hepatoma HepG2 cells, while this effect was not found in the human immortalized non-tumor cell line.…”

Bioactivities and Health Benefits of Mushrooms Mainly from China

“…Inhibition of the growth of tumor cells by inducing of apoptosis and causing cell-cycle arrest [71,72] …”

Iso-suillin Isolated from Suillus luteus, Induces G1Phase Arrest and Apoptosis in Human Hepatoma SMMC-7721 Cells

“…Prenylphenols are a class of natural products. A number of phenolic compounds have been isolated from Albatrellus ovina, including the novel neogrifolin derivatives 3-hydroxyneogrifolin, 1-formylneogrifolin and 1-formyl-3-hydroxyneogrifolin along with grifolin (Ye et al, 2005) and neogrifolin (Nukata et al, 2002;Yuen-Nei Cheung et al, 2005) (Dekermendjian et al, 1997) and suillin (Liu et al, 2009). These compounds have been shown to play important physiological roles, including antioxidant activity, cholesterol metabolism regulation, antibacterial activity, anti-tumor activity and anti-inflammatory activity.…”