Evaluation of active hexose correlated compound (AHCC) in combination with pegylated liposomal doxorubicin for treatment of ovarian cancer

Summary: The objective was to define the mechanism of the growth inhibition of active hexose correlated compound (AHCC) alone and evaluate its activity in combination with pegylated liposomal doxorubicin (PLD). Scientific Methods: In vitro growth inhibition assays were completed with AHCC alone and in combination with PLD in panel of human cancer cell lines and findings confirmed in vivo in an ovarian cancer xenograft mouse model. AHCC mechanism of action was evaluated with immunoblotting and flow cytometry studies. Major Findings: The in vitro growth inhibition assays demonstrated additive activity when AHCC is co-administered with PLD. The combination of AHCC with PLD demonstrated a 64.1% reduction in tumor growth compared to the untreated group (p value = 0.03) and a 31.2% improvement in tumor response with combination regimen compared to PLD alone. No difference in toxicity was observed in the control or treatment groups. An increased expression of Bcl-2 was observed and induction of apoptosis confirmed in presence of AHCC. Conclusions: There is potential improvement in PLD activity when co-administered with AHCC and decrease side effects of PLD. A clinical study to evaluate of the combination of AHCC plus PLD in the treatment of ovarian cancer is being pursued. Industrial Relevance: This study presents an example of the successful integration of a well- known herbal supplement, AHCC, with traditional western medicine cytotoxic agent, pegylated liposomal doxorubicin, for the treatment of recurrent ovarian cancer. In addition to providing evidence of the efficacy of AHCC, the mechanism of improved activity was also investigated. Using a traditional approach this study provides pre-clinical data to support the benefits previously observed and reported in the clinical setting and supports future endeavors to integrate AHCC into standard of care to be given with chemotherapy. . These finding are particularly beneficial in the treatment of recurrent cancer when maintaining a good quality of life during chemotherapy is a priority and allows patients to have a natural, nutritional approach to preventing and managing chemotherapy adverse effects.