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Chaga mushroom may provide a new therapeutic option, as a potential anticancer agent, in the treatment of hepatoma.

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Trichostatin A (TSA), originally developed as an antifungal agent, is one of potent histone deacetylase (HDAC) inhibitors, which are known to cause growth arrest and apoptosis induction of transformed cells, including urinary bladder, breast, prostate, ovary, and colon cancers. However, the effect of HDAC inhibitors on human non-small cell lung cancer cells is not clearly known yet. Herein, we demonstrated that treatment of TSA resulted in a significant decrease of the viability of H157 cells in a dose-dependent manner, which was revealed as apoptosis accompanying with nuclear fragmentation and an increase in sub-G 0 /G 1 fraction. In addition, it induced the expression of Fas/FasL, which further triggered the activation of caspase-8. Catalytic activation of caspase-9 and decreased expression of anti-aptototic Bcl-2 and Bcl-XL proteins were observed in TSA-treated cells. Catalytic activation of caspase-3 by TSA was further confirmed by cleavage of pro-caspase-3 and intracellular substrates, including poly (ADP-ribose) polymerase (PARP) and inhibitor of caspase-activated deoxyribonuclease (ICAD). In addition, a characteristic phenomenon of mitochondrial dysfunction, including mitochondrial membrane potential transition and release of mitochondrial cytochrome c into the cytosol was apparent in TSA-treated cells. Taken together, our data indicate that inhibition of HDAC by TSA induces the apoptosis of H157 cells through signaling cascade of Fas/FasL-mediated extrinsic and mitocondria-mediated intrinsic caspases pathway.

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Glioblastoma is the most common and most aggressive of the primary brain tumors.1,2) With its highly invasive phenotype, glioblastoma diffusely infiltrates various regions of the normal brain, making total surgical removal impossible, and thus patients diagnosed with glioblastoma have a poor prognosis, even in response to multidisciplinary treatment strategies, including surgery, radiotherapy and chemotherapy. 3) Unlike normal cells, the growth of tumor cells is uncontrolled. A strategy of chemotherapy is to change the biological properties of the cancerous cells that lead to apoptosis or to kill the cancer cells. 4) Apoptosis is a physiological mode of cell death that can be selectively triggered by cells in response to a stimulus. Therefore, the induction of apoptosis is a key target of anticancer drugs.Berberine, a well-known alkaloid, was found to be initially isolated from herbs used in traditional Chinese herbal medicine, such as Coptis chinensis and Hydrastis Canadensis. Currently, the predominant clinical uses of berberine preparations include the treatment of bacterial diarrhea, intestinal parasite infections and ocular trachoma infections.5) Other pharmacological effects of berberine, such as its antiarrhythmic, anti-inflammatory, anticancer, immunosuppressive, vasorelaxant and antiproliferative effects, have also been reported.6-10) The chemical structure of berberine chloride, which has a molecular weight of 371.8, is shown in Fig. 1. In recent years, berberine has been examined for anticancer activity, following evidence of its antineoplastic properties. 11)Berberine has also been shown to interact with nucleic acids, especially DNA, in vitro.12) Berberine has the ability to induce apoptosis in human cancer cells, and promyelocytic leukemia HL-60 cells can form berberine complexes with DNA.13) Cell cycle studies showed that berberine induces rapid apoptosis during the S phase of the cell cycle.13) It has also been reported that berberine has dose-dependent effects on the G2/M phase and on the process of apoptosis in Balb/c 3T3 cells.14) However, the effects of berberine on human glioblastoma cells remain unclear. Therefore, we recently focused on human glioblastoma, one of the tumor incidences that has increased extensively worldwide and has become one of the most frequent malignant neoplasms. The purpose of the present study was to investigate the relationship between the antiproliferative activities of berberine and the apoptotic pathway with its molecular mechanism of action in human glioblastoma T98G cells. Berberine is an isoquinoline plant alkaloid with a long history of being used for the treatment of many diseases in Chinese herbal medicine. Berberine has a wide range of biochemical and pharmacological effects, including antitumor activities, but its mechanism of action is not clearly understood. In this study, we investigated that the relationship between the antiproliferative activities of berberine and the apoptotic pathway associated with its molecular mechanism of action in human gliob...