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 12h 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.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis , Terpenes/pharmacology , Animals , Basidiomycota/chemistry , Caspases/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Cytochromes c/metabolism , Down-Regulation , Humans , Mice , Neoplasms/pathology , Proto-Oncogene Proteins c-bcl-2/metabolism , Up-Regulation , bcl-2-Associated X ProteinABSTRACT
Previous work of the authors established the protein expression spectra of D-type cyclins, and found that there were differential expression in nasopharyngeal carcinoma (NPC) biopsies. Using Western Blotting, aberrant overexpression of the cyclinD1 protein in NPC cell lines is reported. CyclinD2 and cyclinD3, the other members of D-type cyclins, were also detected in NPC cell lines. A comparison of the expression patterns in the cell lines, positive or negative in the latent membrane protein 1 (LMP1) encoded by Epstein-Barr virus, revealed that the expression of D-Type cyclin proteins might be increased by EBV-LMP1. The abundance of these proteins showed characteristic variation consistent with a cell- cycle-dependent oscillation and the peak levels expressed in G1 as analyzed by double-parameter flow cytometry. These data suggest that cyclinD1 is essential for cell cycle progression in G1 and may play a role in NPC carcinogenesis.
