Modified arabinoxylan rice bran (MGN-3/Biobran) potentiates apoptosis in cancer cells induced by multiple anti-cancer agents in vitro
aDepartment of Otolaryngology, Charles R. Drew University of Medicine and Science, Los Angeles, CA, United States, bDivision of Basic and Clinical Immunology, University of California, Irvine, CA, United States
AIM: To investigate the potentiating effect of MGN-3/Biobran against apoptosis in cancer cells induced by multiple anti-cancer agents. MGN-3 is an arabinoxylan from rice bran that had been modified by carbohydrate hydrolyzing enzymes from shiitake mushrooms. METHODS: Human myeloid leukemia cells resistant to Adriamycin (HL60/AR) and human metastatic breast cancer cell line (MCF-7) were used in the study. HL60/AR were exposed to MGN-3 (1000 ?g/ml) for 3 hours and subsequently cultured with different concentrations of Adriamycin. Drug sensitivity was determined using MTT assay and drug accumulation was determined by flow cytometry. Breast cancer MCF-7 cells were treated with MGN-3 (100?g/ml) and caffeine (2.5 mM). Cell survival was determined by MTT assay. RESULTS: The inhibitory concentration (IC50) of Adriamycin to HL60/AR cells was 20?M. MGN-3 treatment increased the sensitivity of HL60/AR to Adriamycin (IC50+8?M), representing a 2.5-fold decrease in sensitivity. This effect of MGN-3 on drug sensitization was associated with increased accumulation of the chemotherapeutic agent in tumor cells. The results with respect to MCF-7 cells showed a synergistic effect of caffeine with MGN-3 (percent dead cells was approximately 2-fold greater as compared to either caffeine or MGN-3 alone). CONCLUSION: These findings suggest that MGN-3 is an effective anti-tumor agent in conjunction with multiple anti-cancer agents and it may be considered a potential candidate for clinical use.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in oral session 991 (Synergistic therapies).