Blazeispirol A from Agaricus blazei Fermentation Product Induces Cell Death in Human Hepatoma Hep 3B Cells through Caspase-Dependent and Caspase-Independent Pathways

Graduate Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan, Republic of China.
Journal of Agricultural and Food Chemistry (Impact Factor: 2.91). 03/2011; 59(9):5109-16. DOI: 10.1021/jf104700j
Source: PubMed


Currently, liver cancer is a leading cause of cancer-related death in the world. Hepatocellular carcinoma is the most common type of liver cancer. Previously, it was reported that blazeispirol A (BA) is the most active antihepatoma compound in an ethanolic extract of Agaricus blazei fermentation product. The aim of this study was to understand the antihepatoma mechanism of BA in human liver cancer Hep 3B cells. The results showed that BA inhibited the growth of Hep 3B cells and increased the percentage of cells in sub-G1 phase in a concentration- and time-dependent manner. In addition, BA treatment resulted in DNA fragmentation, caspase-9 and caspase-3 activations, poly(ADP-ribose)polymerase (PARP) degradation, down-regulation of Bcl-2 and Bcl-xL expressions, up-regulation of Bax expression, and disruption of the mitochondrial membrane potential (MMP) in Hep 3B cells. Furthermore, z-VAD-fmk, a caspase inhibitor, did not enhance the viability of BA-treated Hep 3B cells, and BA induced the release of HtrA2/Omi and apoptosis-inducing factor (AIF) from mitochondria into the cytosol. These findings suggested that BA with novel chemopreventive and chemotherapeutic potentials causes both caspase-dependent and caspase-independent cell death in Hep 3B cells.

8 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: This paper is concerned with Hepato-Cellular Carcinoma (HCC) patients treated naturopathic agents. Patients treated with ≥4 agents survived significantly longer than patients treated with ≤3 agents. The great effect is seen in patients treated with at least 4 agents that include Cordyceps sinensis. This greater certainty of patient survival without toxic side effects is significant benefit comparing with the conventional therapy. Treatment of HCC with a regimen of ≥4 agents prepared from natural products is associated with greater certainty of patient survival in a substantial portion of patients. The information dynamic model for certainty of patient survival is derived based on fluid mechanics, where a series of approximate solutions of the flow between two parallel flat walls, one of which is at rest, the other is suddenly accelerated from the rest to a constant velocity are used. The kinetic energy of certainty of patient survival decreases with increasing time, while the potential energy increases with increasing time. Total mechanical energy of patients treated with 4 or more agents is smaller than that treated with 3 or fewer agents. The kinetic energy (potential energy) of patients treated with 4 or more agents decreases (increases) more slower than the kinetic energy (potential energy) of patients treated with 3 or fewer agents.
    No preview · Article · Jan 2012 · Open Journal of Preventive Medicine
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hypothesis. Naturopathic treatment will benefit patients with hepatocellular carcinoma (HCC). STUDY DESIGN: Retrospective analysis of case series of HCC patients treated with naturopathic agents. METHODS: HCC was diagnosed by dynamic computed tomography (CT) imaging and α-fetoprotein (AFP) or PIVKA II, or by histology. Tumor staging was determined by CT. A modified Childs-Pugh scoring was used to assess liver disease. Patients were treated with orally administered combinations of 12 naturopathic agents. Patients were monitored clinically and by CT tumor imaging, serial tumor markers, and liver function tests. RESULTS: Patient characteristics: 101 patients with HCC (67 men and 34 women, age 67.2 ± 8.8 years) were treated for a median of 13.4 months (range 0.8-100.8). Of these 84% had cirrhosis, 63% had hepatitis C virus, 18% had hepatitis B virus, 1% had both, and 9% had metastatic disease. Median modified Childs-Pugh score was 6 (range 3-13). Barcelona Clinic Liver Cancer tumor stages of 0, A, B, C, and D were found in 36%, 25%, 20%, 14%, and 6%, respectively. Median AFP was 40 (range 0-311,000). Median PIVKA II was 59 (0-378,000). Previous treatment was included none (27%), resection with relapse (20%), transarterial chemoembolization (50%), radiofrequency ablation (28%), percutaneous ethanol injection therapy (15%), chemotherapy (14%). Outcomes: Initial treatment was with 2.6 ± 0.8 agents (range 2-4). Overall, patients were treated with 3.7 ± 1.2 agents (range 2-7). There was a significant correlation between number of agents administered and survival (P < .0001). Patients treated with ≥4 agents survived significantly longer than patients treated with ≤3 agents (40.2 vs 6.4 months, P < .0001). This difference could not be attributed to statistically significant differences in severity of liver disease or tumor stage, delay in treatment, previous treatment, concurrent nondrug treatment, or censoring effects. The greatest effect was seen in patients treated with at least 4 agents that included Cordyceps sinensis. This prolonged survival was without toxic side effects and appeared to potentiate the survival benefit of conventional therapy. CONCLUSION: Treatment of HCC with a regimen of ≥4 agents prepared from natural products was associated with prolonged survival in a substantial portion of patients. The data provide level II evidence for the efficacy of naturopathic therapy in HCC.
    No preview · Article · Apr 2012 · Integrative Cancer Therapies
  • [Show abstract] [Hide abstract]
    ABSTRACT: An increasing body of scientific literature suggests that dietary components may exert cancer preventive effects. Tea, soy, cruciferous vegetables and other foods have been investigated for their cancer preventive potential. Some non-edible mushrooms like Reishi (Ganoderma lucidum) have a history use, both alone and in conjunction with standard therapies, for the treatment of various diseases including cancer in some cultures. They have shown efficacy in a number of scientific studies. By comparison, the potential cancer preventive effects of edible mushrooms have been less well-studied. With similar content of putative effective anticancer compounds such as polysaccharides, proteoglycans, steroids, etc., one might predict that edible mushrooms would also demonstrate anticancer and cancer preventive activity. In this review, available data for five commonly-consumed edible mushrooms: button mushrooms (Agaricus bisporus), A. blazei, oyster mushrooms (Pleurotus ostreatus), shiitake mushrooms (Lentinus edodes), and maitake (Grifola frondosa) mushrooms is discussed. The results of animal model and human intervention studies, as well as supporting in vitro mechanistic studies are critically evaluated. Weaknesses in the current data and topics for future work are highlighted.
    No preview · Article · May 2012 · Anti-cancer agents in medicinal chemistry
Show more