Bacteria as a treasure house of secondary metabolites with anticancer potential

Chakrabhavi Dhananjaya Mohan; Shobith Rangappa; S Chandra Nayak; Ragi Jadimurthy; Lingzhi Wang; Gautam Sethi; Manoj Garg; Kanchugarakoppal S Rangappa

doi:10.1016/j.semcancer.2021.05.006

Bacteria as a treasure house of secondary metabolites with anticancer potential

Semin Cancer Biol. 2022 Nov;86(Pt 2):998-1013. doi: 10.1016/j.semcancer.2021.05.006. Epub 2021 May 9.

Authors

Chakrabhavi Dhananjaya Mohan¹, Shobith Rangappa², S Chandra Nayak³, Ragi Jadimurthy¹, Lingzhi Wang⁴, Gautam Sethi⁵, Manoj Garg⁶, Kanchugarakoppal S Rangappa⁷

Affiliations

¹ Department of Studies in Molecular Biology, University of Mysore, Manasagangotri, Mysore, 570006, India.
² Adichunchanagiri Institute for Molecular Medicine, Adichunchanagiri University, BG Nagara, 571448, Nagamangala Taluk, India.
³ Department of Studies in Biotechnology, University of Mysore, Manasagangotri, Mysore, 570006, India.
⁴ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
⁵ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore.
⁶ Amity Institute of Molecular Medicine and Stem Cell Research, Amity University, Uttar Pradesh, Noida, 201313, India.
⁷ Institution of Excellence, Vijnana Bhavan, University of Mysore, Manasagangotri, Mysore, 570006, India. Electronic address: rangappaks@ioe.uni-mysore.ac.in.

PMID: 33979675
DOI: 10.1016/j.semcancer.2021.05.006

Abstract

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.

Keywords: Anticancer drugs; Antitumor antibiotics; Bacteria-derived antitumor agents; Bacterial metabolites; Metagenomics; Natural compounds.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents* / pharmacology
Antineoplastic Agents* / therapeutic use
Bacteria
Biological Products* / pharmacology
Biological Products* / therapeutic use
Fungi / metabolism
Humans
Neoplasms* / drug therapy

Substances

Antineoplastic Agents
Biological Products