The Key Laboratory of Biomedical Information Engineering, Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas, United States.
Curr Med Chem. 2019;26(10):1849-1873. doi: 10.2174/0929867324666170523123655.
Gossypol, a natural product extracted from the seed, roots, and stem of cotton, was initially used as a male contraceptive but was subsequently investigated as a novel antitumor agent. This review depicts the current status of gossypol and its derivatives as novel antitumor agents as well as presents their preparation and characteristics, especially of some gossypol Schiff bases, through quantitative and structural analysis. The main attractive target sites of gossypol and its derivatives are Bcl-2 family proteins containing the anti-apoptosis proteins Bcl-2 and Bcl-XL. The molecular mechanism of gossypol analogs not only involves cell apoptosis but also autophagy, cell cycle arrest, and other abnormal cellular phenomena. Gossypol and its derivatives exert antitumor effects on different cancer types in vitro and in vivo, and demonstrate synergistic effects with other chemo- and radio- therapeutic treatments. In addition, several nanocarriers have been designed to load gossypol or its derivatives in order to expand the range of their applications and evaluate their combination effects with other anti-tumor agents. This review may serve as a reference for the rational application of gossypol analogs as anti-tumor agents.
棉酚是从棉花的种子、根和茎中提取的天然产物，最初被用作男性避孕药，但后来被作为一种新型抗肿瘤药物进行了研究。本综述描述了棉酚及其衍生物作为新型抗肿瘤药物的现状，并通过定量和结构分析介绍了它们的制备和特性，特别是一些棉酚席夫碱。棉酚及其衍生物的主要吸引人的靶位是包含抗凋亡蛋白 Bcl-2 和 Bcl-XL 的 Bcl-2 家族蛋白。棉酚类似物的分子机制不仅涉及细胞凋亡，还涉及自噬、细胞周期停滞和其他异常细胞现象。棉酚及其衍生物在体外和体内对不同类型的癌症具有抗肿瘤作用，并与其他化疗和放疗治疗具有协同作用。此外，还设计了几种纳米载体来负载棉酚或其衍生物，以扩大其应用范围，并评估其与其他抗肿瘤药物的联合作用。本综述可为合理应用棉酚类似物作为抗肿瘤药物提供参考。
