Abstract
Abstract Objective: Hepatocellular carcinoma is one of the most common cancers in the world and one of the most lethal. MGN-3/Biobran, derived from rice bran hemicelluloses, has been reported to possess a strong anticancer effect against several neoplasms. In the current study, we examined the protective effect of MGN-3/Biobran against N-nitrosodiethylamine (NDEA) and carbon tetrachloride (CCl4)-induced hepatocarcinogenesis in rats and studied the molecular mechanisms underlying its effect. Materials and Methods: Male albino rats received carcinogen NDEA (200 mg/kg body weight) single dose i.p. plus promoter CCl4 (3 ml/kg b.w.) weekly s.c. for 6 weeks. Another group of rats were treated with MGN-3/Biobran (25mg/Kg b.w.) 5 times/week i.p. for 2 weeks prior to receiving carcinogens and continued for 20 weeks. Tumor incidence, histopathology, body and liver weight, liver marker enzymes, cell cycle progression, cell proliferation and apoptotic-related markers at mRNA and protein expression levels were quantitatively determined. Results: Rats exposed to carcinogens alone showed loss of liver architecture, and proliferative and neoplastic changes. This group also showed marked decrease in body weight, increase in liver weight, and elevation in the levels of hepatic diagnostic markers: serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (gamma GT). In contrast, rats pretreated with MGN-3/ Biobran and subsequently exposed to carcinogens showed significant reduction in liver tumor incidence, marked decrease in the percentage of pre-neoplastic foci in hepatic parenchyma, and inhibition in the development of hepatocellular carcinoma. MGN-3/ Biobran treatment also maintained AST, ALT, ALP, and gamma GT levels close to normal values. In addition, MGN-3/Biobran treatment was associated with marked increase in both the cell cycle sub-G0/G1 population and AnnexinV-binding. The molecular studies at mRNA and protein expression levels in the liver tissues demonstrated that MGN-3/ Biobran reversed carcinogen induced suppression in the level of IkappaB-alpha (IκB-α), downregulated the expression of the nuclear factor kappa-B (NF-κBp65) and Bcl2, upregulated the expression of p53, Bax, caspases-3 and markedly increased Bax/Bcl2 ratio. Conclusion: This study concluded that MGN-3/ Biobran inhibited hepatocarcinogenesis induced by NDEA and CCI4 via induction of apoptosis and inhibition of cancer cell proliferation. MGN-3/ Biobran may be a promising chemopreventive agent for liver carcinogenesis. Biobran /MGN-3 was provided by Daiwa Pharmaceutical Co., Ltd. Tokyo, Japan. Citation Format: Nariman K. Badr El-Din, Doaa A. Ali, Reem Othman, Mamdooh Ghoneum. Prevention of hepatocarcinogenesis in rats by arabinoxylan rice bran, MGN-3/Biobran. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5259.
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