Department of Zoology, Faculty of Science, University of Mansoura, Mansoura, Egypt.
Department of Zoology, Faculty of Science, University of Mansoura, Mansoura, Egypt.
Biomed Pharmacother. 2020 Jun;126:110064. doi: 10.1016/j.biopha.2020.110064. Epub 2020 Apr 8.
Hepatocellular carcinoma (HCC) is one of the most common cancers in the world and one of the most lethal. MGN-3/Biobran is a natural product derived from rice bran hemicelluloses and has been reported to possess a potent anticancer effect in a clinical study of patients with HCC. The current study examines the mechanisms by which Biobran protects against chemically induced hepatocarcinogenesis in rats. The chemical carcinogen used in this study is N-nitrosodiethylamine (NDEA) plus carbon tetrachloride (CCl). Rats were treated with this carcinogen, and the animals were pretreated or posttreated with Biobran via intraperitoneal injections until the end of the experiment. Treatment with Biobran resulted in: 1) significant alleviation of liver preneoplastic lesions towards normal hepatocellular architecture in association with inhibition of collagen fiber deposition; 2) arrest of cancer cells in the sub-G1 phase of the cell cycle; 3) increased DNA fragmentation in cancer cells; 4) down-regulated expression of Bcl-2 and up-regulated expression of p53, Bax, and caspase-3; and 5) protection against carcinogen-induced suppression of IkappaB-alpha (IκB-α) mRNA expression and inhibition of nuclear factor kappa-B (NF-κB/p65) expression. Additionally, the effect of Biobran treatment was found to be more significant when supplemented prior to carcinogen-induced hepatocarcinogenesis as compared to posttreatment. We conclude that Biobran inhibits hepatocarcinogenesis in rats by mechanisms that include induction of apoptosis, inhibition of inflammation, and suppression of cancer cell proliferation. Biobran may be a promising chemopreventive and chemotherapeutic agent for liver carcinogenesis.
肝细胞癌(HCC)是世界上最常见的癌症之一,也是最致命的癌症之一。MGN-3/Biobran 是一种源自米糠半纤维素的天然产物,在一项 HCC 患者的临床研究中已被报道具有强大的抗癌作用。本研究探讨了 Biobran 预防大鼠化学诱导肝癌发生的机制。本研究中使用的化学致癌物是 N-亚硝基二乙胺(NDEA)加四氯化碳(CCl)。用这种致癌剂处理大鼠,并用腹腔内注射 Biobran 对动物进行预处理或后处理,直到实验结束。Biobran 的治疗导致:1)显著减轻肝前病变,使肝组织结构恢复正常,同时抑制胶原纤维沉积;2)阻止癌细胞进入细胞周期的 sub-G1 期;3)增加癌细胞中的 DNA 片段化;4)下调 Bcl-2 的表达,上调 p53、Bax 和 caspase-3 的表达;5)防止致癌物诱导的 IkappaB-alpha(IκB-α)mRNA 表达抑制和核因子 kappa-B(NF-κB/p65)表达抑制。此外,与在致癌诱导的肝癌发生后进行治疗相比,在致癌诱导的肝癌发生前进行 Biobran 治疗的效果更为显著。我们得出结论,Biobran 通过诱导细胞凋亡、抑制炎症和抑制癌细胞增殖等机制抑制大鼠肝癌的发生。Biobran 可能是一种有前途的肝癌化学预防和化学治疗药物。