Hua Fang, Shang Shuang, Hu Zhuo-Wei
a Immunology and Cancer Pharmacology Group, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100050 , China.
J Asian Nat Prod Res. 2017 Apr;19(4):305-313. doi: 10.1080/10286020.2017.1304385. Epub 2017 Mar 28.
Natural products are an important original source of many widely used drugs, including anti-cancer drugs. Early research efforts for seeking anti-cancer therapy from the natural products are mainly focused on the compounds with cytotoxicity capability. The good examples include vinblastine, vincristine, the camptothecin derivatives; topotecan, irinotecan, epipodophyllotoxin derivatives and paclitaxel. In a recent decade, the fundamental progression has been made in the understanding of molecular and cellular mechanisms regarding tumor initiation, metastasis, therapeutic resistance, immune escape, and relapse, which provide a great opportunity for the development of new mechanism-based anticancer drugs, especially drugs against new molecular and cellular targets. Autophagy, a critical cell homeostasis mechanism and promising drug target involved in a verity of human diseases including cancer, can be modulated by many compounds derived from natural products. In this review, we'll give a short introduction of autophagy and discuss the roles of autophagy in the tumorigenesis and progression. And then, we summarize the accumulated evidences to show the anti-tumor effects of several compounds derived from natural products through modulation of autophagy activity.
天然产物是许多广泛使用的药物(包括抗癌药物)的重要原始来源。早期从天然产物中寻找抗癌疗法的研究工作主要集中在具有细胞毒性的化合物上。典型的例子包括长春碱、长春新碱、喜树碱衍生物;拓扑替康、伊立替康、鬼臼毒素衍生物和紫杉醇。在最近十年中,在对肿瘤发生、转移、治疗耐药性、免疫逃逸和复发的分子和细胞机制的理解方面取得了根本性进展,这为开发基于新机制的抗癌药物,特别是针对新分子和细胞靶点的药物提供了巨大机会。自噬是一种关键的细胞稳态机制,也是涉及包括癌症在内的多种人类疾病的有前景的药物靶点,它可以被许多天然产物衍生的化合物所调节。在这篇综述中,我们将简要介绍自噬,并讨论自噬在肿瘤发生和进展中的作用。然后,我们总结已积累的证据,以展示几种天然产物衍生的化合物通过调节自噬活性所产生的抗肿瘤作用。