Bacteria as a treasure house of secondary metabolites with anticancer potential
Bacteria as a treasure house of secondary metabolites with anticancer potential
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DOI：
10.1016/j.semcancer.2021.05.006
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发表时间：
2022-10-19
影响因子：
14.5
通讯作者：
Rangappa，Kanchugarakoppal S.
中科院分区：
文献类型：
--
作者：
Mohan，Chakrabhavi Dhananjaya;Rangappa，Shobith;Rangappa，Kanchugarakoppal S.
癌症是全球主要杀手之首，预计到2040年，每年的死亡率将达到1640万。人类患有大约200种不同类型的癌症，其中许多癌症只有少量批准的治疗药物。此外，几种类型的主要癌症在晚期被诊断出来，因此现有的治疗方法对它们的疗效有限，并导致预后不良。因此，必须开发新的有效的抗癌药物来对抗癌症驱动的致死性。天然来源如细菌、植物、真菌和海洋微生物一直是抗癌剂的取之不尽的来源。值得注意的是，已经从不同的细菌来源中分离出超过13，000种具有不同药理学特性的天然化合物。在本文中，我们讨论了天然产物的重要性，特别强调了细菌代谢产物对癌症治疗的重要性。随后，我们全面讨论了各种来源，作用机制，毒性问题，和脱靶效应的临床使用的抗癌药物（如放线菌素D，博莱霉素，卡非佐米，阿霉素，伊沙匹隆，丝裂霉素C，喷司他丁，雷帕霉素类似物，和罗米地辛）已来自不同的细菌。此外，我们还讨论了一些主要的次级代谢产物（抗霉素，查曲菌素，elsamicins，格尔德霉素，莫能菌素，普卡霉素，灵菌红素，rebeccamycin，盐霉素和salinosporamide），目前在临床试验中或已在临床前模型中证明了有效的抗癌活性。此外，我们还阐述了宏基因组学在药物发现中的应用，并简要介绍了通过宏基因组学方法鉴定的抗癌药物（苔藓抑素1和ET-743）。
Cancer stands in the frontline among leading killers worldwide and the annual mortality rate is expected to reach 16.4 million by 2040. Humans suffer from about 200 different types of cancers and many of them have a small number of approved therapeutic agents. Moreover, several types of major cancers are diagnosed at advanced stages as a result of which the existing therapies have limited efficacy against them and contribute to a dismal prognosis. Therefore, it is essential to develop novel potent anticancer agents to counteract cancer-driven lethality. Natural sources such as bacteria, plants, fungi, and marine microorganisms have been serving as an inexhaustible source of anticancer agents. Notably, over 13,000 natural compounds endowed with different pharmacological properties have been isolated from different bacterial sources. In the present article, we have discussed about the importance of natural products, with special emphasis on bacterial metabolites for cancer therapy. Subsequently, we have comprehensively discussed the various sources, mechanisms of action, toxicity issues, and off-target effects of clinically used anticancer drugs (such as actinomycin D, bleomycin, carfilzomib, doxorubicin, ixabepilone, mitomycin C, pentostatin, rapalogs, and romidepsin) that have been derived from different bacteria. Furthermore, we have also discussed some of the major secondary metabolites (antimycins, chartreusin, elsamicins, geldanamycin, monensin, plicamycin, prodigiosin, rebeccamycin, salinomycin, and salinosporamide) that are currently in the clinical trials or which have demonstrated potent anticancer activity in preclinical models. Besides, we have elaborated on the application of metagenomics in drug discovery and briefly described about anticancer agents (bryostatin 1 and ET-743) identified through the metagenomics approach.