Abstract 3932: Enhancing the effectiveness of radiation therapy with arabinoxylan rice bran (MGN-3/ Biobran) in mouse bearing solid tumor

Abstract

Abstract Purpose: Enhancing tumor radio-responsiveness via natural radiosensitizer agents is a promising approach for improving the efficacy of radiation therapy. In the present work, we examine the radiosensitizing effect of arabinoxylan rice bran (MGN-3/Biobran), a potent biological response modifier, on fractionated X-ray irradiation of Ehrlich solid tumor-bearing mice and elucidate the molecular mechanism underlying its effect. Materials and Methods: Swiss albino mice were inoculated in the thigh with Ehrlich ascites carcinoma cells. Mice bearing tumors were treated with Biobran (40mg/kg/day, i.p.), 5 days/week, beginning on day 11 post inoculation until day 30. Mice received X-ray ionizing radiation (IR) with or without Biobran at a dose level 6 gray (Gy) divided into three fractionated doses (2 Gy) each with a dose rate of 0.85 Gy/min on days 12, 14 or 16 post inoculation. Tumor growth was measured; cell cycle analysis, apoptosis, and apoptotic regulator expression were analyzed by flow cytometry and RT-PCR; DNA fragmentation was detected by gel electrophoresis; and safety parameters were evaluated. Results: IR-induced tumor regression was enhanced in mice treated with Biobran. Tumor weight was reduced relative to control by 31% for IR alone, by 46% for Biobran alone, and by 57% for co-treatment. Relative to control, Biobran alone and IR alone arrested the hypodiploid cells in the sub-G1-phase by 102% and 85%, respectively, signifying apoptosis, while co-treatment enhanced IR induced apoptosis by 123% and maximized the apoptosis/proliferation ratio. Co-treatment also potentiated early apoptosis in cancer cells as detected by Annexin V/PI and augmented DNA laddering pattern. In addition, co-treatment profoundly upregulated protein and mRNA expression of p53, Bax, and caspase-3 and downregulated Bcl-2 expression. Bax/Bcl-2 ratio was increased relative to control by 3.4 fold for IR alone and maximized at 9.5 fold for co-treatment. With regard to safety parameters, co-treatment markedly modulated the decrease in body weight and the increase of liver and spleen weight of mice treated with IR alone, and it decreased IR-induced elevation of serum enzyme levels (AST, ALT, and GGT). Conclusion: This study concludes that MGN-3/Biobran potently enhances radiation therapy-induced tumor regression by potentiating apoptosis and minimizing toxicities related to radiation therapy. MGN-3/Biobran may have utility in human cancer patients undergoing radiotherapy and could warrant clinical trials. MGN-3/Biobran was supplied by Daiwa Pharmaceutical Co., Ltd., Japan. Citation Format: Nariman K. Badr El-Din, Sayed K. Areida, Kavan O. Ahmed, Mamdooh Ghoneum. Enhancing the effectiveness of radiation therapy with arabinoxylan rice bran (MGN-3/ Biobran) in mouse bearing solid tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3932.