Wei Feng, Nian Qing, Zhao Maoyuan, Wen Yueqiang, Yang Yi, Wang Jundong, He Zhelin, Chen Xiaoyan, Yin Xiang, Wang Jian, Ma Xiao, Chen Yu, Feng Peimin, Zeng Jinhao
Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; School of Clinical Medicine, Chengdu University of Chinese Medicine, Chengdu 610075, 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, China.
Biomed Pharmacother. 2023 Nov;167:115473. doi: 10.1016/j.biopha.2023.115473. Epub 2023 Sep 15.
Colorectal cancer (CRC) is a globally prevalent malignancy with a high potential for metastasis. Existing cancer treatments have limitations, including drug resistance and adverse effects. Researchers are striving to develop effective therapies to address these challenges. Impressively, contemporary research has discovered that many natural products derived from foods, plants, insects, and marine invertebrates can suppress the progression, metastasis, and invasion of CRC. In this review, we conducted a comprehensive search of the CNKI, PubMed, Embase, and Web of Science databases from inception to April 2023 to evaluate the efficacy of natural products targeting mitochondria to fight against CRC. Mitochondria are intracellular energy factories involved in cell differentiation, signal transduction, cell cycle regulation, apoptosis, and tumorigenesis. The identified natural products have been classified and summarized based on their mechanisms of action. These findings indicate that natural products can induce apoptosis in colorectal cancer cells by inhibiting the mitochondrial respiratory chain, ROS elevation, disruption of mitochondrial membrane potential, the release of pro-apoptotic factors, modulation of the Bcl-2 protein family to facilitate cytochrome c release, induction of apoptotic vesicle activity by activating the caspase protein family, and selective targeting of mitochondrial division. Furthermore, diverse apoptotic signaling pathways targeting mitochondria, such as the MAPK, p53, STAT3, JNK and AKT pathway, have been triggered by natural products. Natural products such as diosgenin, allopurinol, and clausenidin have demonstrated low toxicity, high efficacy, and multi-targeted properties. Mitochondria-targeting natural products have great potential for overcoming the challenges of CRC therapy.
结直肠癌（CRC）是一种在全球普遍存在的恶性肿瘤，具有很高的转移潜力。现有的癌症治疗方法存在局限性，包括耐药性和不良反应。研究人员正在努力开发有效的治疗方法来应对这些挑战。令人印象深刻的是，当代研究发现，许多源自食物、植物、昆虫和海洋无脊椎动物的天然产物可以抑制结直肠癌的进展、转移和侵袭。在这篇综述中，我们对中国知网、PubMed、Embase和Web of Science数据库进行了全面检索，检索时间跨度从建库至2023年4月，以评估靶向线粒体的天然产物对抗结直肠癌的疗效。线粒体是参与细胞分化、信号转导、细胞周期调控、细胞凋亡和肿瘤发生的细胞内能量工厂。已根据其作用机制对鉴定出的天然产物进行了分类和总结。这些发现表明，天然产物可通过抑制线粒体呼吸链、升高活性氧、破坏线粒体膜电位、释放促凋亡因子、调节Bcl-2蛋白家族以促进细胞色素c释放、激活半胱天冬酶蛋白家族以诱导凋亡小泡活性以及选择性靶向线粒体分裂来诱导结直肠癌细胞凋亡。此外，天然产物还触发了多种靶向线粒体的凋亡信号通路，如MAPK、p53、STAT3、JNK和AKT通路。薯蓣皂苷元、别嘌呤醇和吴茱萸次碱等天然产物已显示出低毒性、高效性和多靶点特性。靶向线粒体的天然产物在克服结直肠癌治疗挑战方面具有巨大潜力。
