Abstract 5259: Prevention of hepatocarcinogenesis in rats by arabinoxylan rice bran, MGN-3/Biobran

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.

Evidence-Based Review of BioBran/MGN-3 Arabinoxylan Compound as a Complementary Therapy for Conventional Cancer Treatment

“…Sixteen articles were excluded with reasons as follows: duplication (5), 11 - 15 not cancer focused (7), 16 - 22 not primary study (3), 23 - 25 and 1 case report article published in Japanese was also excluded. 26 Thirty full-text articles and 2 conference abstracts were included in this review, consisting of 7 in vitro studies; 27 - 33 1 article reporting results from both in vitro and in vivo studies; 34 7 in vivo studies; 35 - 41 6 clinical case reports; 42 - 47 and 11 clinical studies, 48 - 58 with one of them also including case reports of selected follow-up patients. 48 The literature search flow is summarized in Figure 1 .…”

“…MGN-3 treated rats were also able to maintain close to normal levels of hepatic diagnostic markers. 41 …”

“…Since concentrations of MGN-3 used in some of in vitro studies were very high (500-1000 μg/mL), 28 , 29 , 31 , 33 it is unclear whether these concentrations can be of clinical relevance. Although the MGN-3 dosages (5-50 mg/kg/BW) used for in vivo studies 34 , 35 , 37 - 41 were more closely matched to the typical dosage used in human studies, without understanding of the pharmacokinetics of MGN-3, questions remain whether the higher bioavailability via intraperitoneal injection in some animal studies 36 - 41 can be applicable to humans.…”

Chemopreventive Activity of MGN-3/Biobran Against Chemical Induction of Glandular Stomach Carcinogenesis in Rats and Its Apoptotic Effect in Gastric Cancer Cells

“…This includes SEC tumor, 18 , 32 neuroblastoma, 33 and liver cancer. 34 In addition, the synergistic effect of Biobran with conventional therapies (CT) for the treatment of hepatocellular carcinoma patients has been shown to result in greater reduction in tumor size, less recurrence of cancer, and higher survival rate, as compared with patients treated with CT alone. 19 Markus et al also described a successful treatment with full recovery of patient with metastatic hemangiopericytoma posttreatment with Biobran.…”

Comparative Rice Bran Metabolomics across Diverse Cultivars and Functional Rice Gene–Bran Metabolite Relationships

“…Rice bran bioactive components include, but are not limited to γ-oryzanol [15], tocopherols, tocotrienols [16], carotenoids [17], γ-aminobutyric acid [18], octacosanol [19], squalene [20], unsaturated fatty acids [21], phytosterols, and phenolic compounds [22]. Dietary consumption of rice bran was shown to be feasible and tolerable to increase key nutrients and fiber intakes in children and adults [11,23,24,25], and to provide health-promoting properties in the prevention and control of major chronic diseases, such as diabetes [26], chronic inflammation [27], and cardiovascular disease [25,28], as well as cancers of the colon, liver, prostate, and breast [11,24,29,30]. Until recently, rice bran has been largely under-valued and under-utilized for nutritional and medicinal applications [31], and this promising food has not received attention from rice breeders when compared to other traits of agronomic importance (e.g., yield, disease resistance) [32].…”