IF 3.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Nourhan M. Abdelmaksoud, Ahmed I. Abulsoud, Tamer M. Abdelghany, Shereen Saeid Elshaer, Ahmed Samaha, Nadine W. Maurice, Sherine Maher Rizk, Mahmoud A. Senousy
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引用次数: 0

摘要

大肠癌(CRC)是全球发病率第三高的癌症。虽然化疗仍是标准的治疗方法,但天然产品已成为一种很有前景的替代疗法。其中,天然类黄酮芹菜素因其在各种癌症中的促氧化和抗氧化特性而备受关注。本研究旨在通过靶向线粒体SIRT3、HMGB1和beclin 1介导的自噬,评估芹菜素在小鼠CRC模型中治疗CRC的潜在影响。我们每周一次腹腔注射 20 毫克/千克二甲基肼(DMH),连续 20 周诱导 C57BL/6 小鼠患上 CRC。研究开始 6 周后,芹菜素以 25 毫克/千克和 50 毫克/千克的剂量通过口服灌胃的方式在胃内同时给药,直到第 20 周结束。结果显示,在 DMH 诱导的 CRC 中,体重明显下降、结肠缩短和腹泻被认为是 CRC 的标志。此外,组织病理学检查显示,DMH 治疗组出现了发育不良的变化,而芹菜素治疗的 CRC 组未发现发育不良。重要的是,与 DMH 处理组相比,DMH 处理组动物服用芹菜素后,SIRT3 和 MnSOD 的表达水平显著降低,LC3-II 在任一剂量下均显著升高,MDA、c-JNK、HMGB1 和 beclin 1 的水平则呈剂量依赖性显著升高。总之,芹菜素在抑制 DMH 诱导的 CRC 方面可能具有良好的作用。芹菜素通过抑制 SIRT3 的基因表达,进而抑制其靶标 MnSOD 的基因表达,从而产生促氧化活性,导致活性氧(ROS)和脂质过氧化增加。释放的 ROS 又会通过提高 HMGB1、beclin 1 和 LC3-II 蛋白水平,激活 JNK 介导的自噬。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Targeting the SIRT3/MnSOD and JNK/HMGB1/Beclin 1 Axes: Role of Apigenin in Multifaceted Metabolic Intervention in Colorectal Cancer

Targeting the SIRT3/MnSOD and JNK/HMGB1/Beclin 1 Axes: Role of Apigenin in Multifaceted Metabolic Intervention in Colorectal Cancer

Colorectal cancer (CRC) is the third most prevalent cancer worldwide. While chemotherapy remains the standard treatment approach, natural products have emerged as a promising alternative. Among these, apigenin, a natural flavonoid, has garnered significant attention due to its pro-oxidant and antioxidant properties in various types of cancer. This study aimed to assess the potential impact of apigenin in CRC treatment by targeting mitochondrial SIRT3, HMGB1, and beclin 1-mediated autophagy in a mouse model of CRC. We administered 20 mg/kg of dimethyl hydrazine (DMH) intraperitoneally once weekly for 20 weeks to induce CRC in C57BL/6 mice. After 6 weeks of initiating the study, apigenin was intragastrically co-administered by oral gavage at 25 and 50 mg/kg until the end of week 20. The results revealed significant weight loss, shortening of the colon, and diarrhea in DMH-induced CRC, which are considered the marks of CRC. In addition, histopathological examination revealed dysplastic changes in the DMH-treated group, while no dysplasia was found in the apigenin-treated CRC groups. Importantly, the administration of apigenin to DMH-treated animals has led to a significant reduction of SIRT3 and MnSOD expression levels with a significant increase in LC3-II at either dose and a significant dose-dependent increase in the levels of MDA, c-JNK, HMGB1, and beclin 1 compared to the DMH-treated group. In conclusion, apigenin may have a promising role in suppressing DMH-induced CRC. It elicits a pro-oxidant activity by suppressing the gene expression of SIRT3 and subsequently, its target MnSOD, resulting in increased reactive oxygen species (ROS) and lipid peroxidation. The released ROS, in turn, activates JNK-mediated autophagy by enhancing HMGB1, beclin 1, and LC3-II protein levels.

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来源期刊
CiteScore
5.80
自引率
2.80%
发文量
277
审稿时长
6-12 weeks
期刊介绍: The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.
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