Zhao Maoyuan, Yang Yi, Nian Qing, Shen Caifei, Xiao Xiaolin, Liao Wenhao, Zheng Qiao, Zhang Gang, Chen Nianzhi, Gong Daoyin, Tang Jianyuan, Wen Yueqiang, Zeng Jinhao
Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, PR China.
Department of Blood Transfusion, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, PR China.
Phytomedicine. 2023 Feb;110:154608. doi: 10.1016/j.phymed.2022.154608. Epub 2022 Dec 18.
Mitochondria are the energy factories of cells with the ability to modulate the cell cycle, cellular differentiation, signal transduction, growth, and apoptosis. Existing drugs targeting mitochondria in cancer treatment have disadvantages of drug resistance and side effects. Phytochemicals, which are widely found in plants, are bioactive compounds that could facilitate the development of new drugs for gastric cancer. Studies have shown that some phytochemicals can suppress the development of gastric cancer.
We searched for data from PubMed, China National Knowledge Infrastructure, Web of Science, and Embase databases from initial establishment to December 2021 to review the mechanism by which phytochemicals suppress gastric cancer cell growth by modulating mitochondrial function. Phytochemicals were classified and summarized by their mechanisms of action.
Phytochemicals can interfere with mitochondria through several mechanisms to reach the goal of promoting apoptosis in gastric cancer cells. Some phytochemicals, e.g., daidzein and tetrandrine promoted cytochrome c spillover into the cytoplasm by modulating the members of the B-cell lymphoma-2 protein family and induced apoptotic body activity by activating the caspase protein family. Phytochemicals (e.g., celastrol and shikonin) could promote the accumulation of reactive oxygen species and reduce the mitochondrial membrane potential. Several phytochemicals (e.g., berberine and oleanolic acid) activated mitochondrial apoptotic submission via the phosphatidylinositol-3-kinase/Akt signaling pathway, thereby triggering apoptosis in gastric cancer cells. Several well-known phytochemicals that target mitochondria, including berberine, ginsenoside, and baicalein, showed the advantages of multiple targets, high efficacy, and fewer side effects.
Phytochemicals could target the mitochondria in the treatment of gastric cancer, providing potential directions and evidence for clinical translation. Drug discovery focused on phytochemicals has great potential to break barriers in cancer treatment.
线粒体是细胞的能量工厂，具有调节细胞周期、细胞分化、信号转导、生长和凋亡的能力。现有用于癌症治疗的靶向线粒体的药物存在耐药性和副作用的缺点。植物化学物质广泛存在于植物中，是具有生物活性的化合物，有助于开发治疗胃癌的新药。研究表明，一些植物化学物质可以抑制胃癌的发展。
我们检索了从最初建立到2021年12月的PubMed、中国知网、Web of Science和Embase数据库中的数据，以综述植物化学物质通过调节线粒体功能抑制胃癌细胞生长的机制。植物化学物质根据其作用机制进行分类和总结。
植物化学物质可通过多种机制干扰线粒体，以达到促进胃癌细胞凋亡的目的。一些植物化学物质，如大豆苷元和粉防己碱，通过调节B细胞淋巴瘤-2蛋白家族成员促进细胞色素c溢出到细胞质中，并通过激活半胱天冬酶蛋白家族诱导凋亡小体活性。植物化学物质（如雷公藤红素和紫草素）可促进活性氧的积累并降低线粒体膜电位。几种植物化学物质（如黄连素和齐墩果酸）通过磷脂酰肌醇-3-激酶/蛋白激酶B信号通路激活线粒体凋亡程序，从而触发胃癌细胞凋亡。几种著名的靶向线粒体的植物化学物质，包括黄连素、人参皂苷和黄芩苷，显示出多靶点、高效和副作用少的优点。
植物化学物质可靶向线粒体治疗胃癌，为临床转化提供潜在方向和证据。专注于植物化学物质的药物研发在突破癌症治疗障碍方面具有巨大潜力。
