Abstract 5312: Biobran/MGN-3, arabinoxylan from rice bran, sensitizes breast adenocarcinoma tumor cells to paclitaxol in mice

Abstract

Abstract Purpose: While chemotherapy is considered the cornerstone of treatment for various types of cancers, the efficacy of chemotherapeutic agents can be restricted by dose-limiting toxicities. Therefore, there is increasing interest in identifying agents that may increase the sensitivity of cancer cells to conventional chemotherapeutic agents. We have shown that Biobran/MGN-3 sensitizes different breast cancer cell lines towards paclitaxel (taxol) In vitro. The objective of this study is to examine the chemosensitizing ability of Biobran/MGN-3 in breast adenocarcinoma in vivo and its mechanism of action. Materials and Methods: Mice were transplanted subcutaneously with Ehrlich ascites carcinoma (EAC) cells, a breast adenocarcinoma of mouse origin. Mice bearing solid tumors were treated with Biobran/MGN-3 and/or paclitaxel. Tumor growth was monitored for 30 days, cell cycle distribution was analyzed using flow cytometry of propidium iodide(PI)-stained cells. Tumor cell proliferation, DNA damage, and apoptosis were quantitatively evaluated by flow cytometry and examined by light and electron microscopy. Results: Co-treatment of tumor bearing mice with Biobran/MGN-3 + paclitaxel resulted in a marked inhibition of tumor growth: tumor weight was reduced by 93% of control (p < 0.01), which represents a 3.7 fold decrease as compared to tumor weight of paclitaxel alone. In addition, following co-treatment, 20% of the animals showed complete tumor regression. Inhibition of tumor growth was associated with a decrease in cell proliferation by 43%, elevation of DNA damage by 76%, and an enhancement of the apoptotic tumor cells by 157%, of control values (p<0.01). Cell cycle analysis showed a marked increase in the sub-G0/G1 population (hypodiploid DNA content), which is a hallmark of apoptosis, by 3.6 fold of control group and 1.8 fold of paclitaxel group. AnnexinV-PI confirmed the potential increase of apoptosis in tumor cells. Concomitant treatment of Biobran/MGN-3 + paclitaxel also increased the number of infiltrating CD4+ and CD8+ T cells within the tumor, down-regulated Ki67 expression in the tumor cells, and significantly maximized the Apoptosis/Proliferation ratio. Light and electron microscopy studies indicated the mechanism of apoptosis rather than necrosis in the inhibition of tumor tissues of mice treated with Biobran/MGN-3 + paclitaxel. Conclusion:This study demonstrated that treatment with Biobran/MGN-3 markedly improved the efficacy of paclitaxel therapy. These results suggest that Biobran/MGN-3 is an effective chemosensitizer in vivo and may represent a novel adjuvant for the treatment of breast cancer. Biobran/MGN-3 was provided by Daiwa Pharmaceutical Co., Ltd. Tokyo, Japan. Citation Format: Nariman K. Badr El-Din, Doaa A. Ali, Mai Alaa El-Dein, Mamdooh Ghoneum. Biobran/MGN-3, arabinoxylan from rice bran, sensitizes breast adenocarcinoma tumor cells to paclitaxol in mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5312. doi:10.1158/1538-7445.AM2015-5312