Bacteria as a treasure house of secondary metabolites with anticancer potential
Chakrabhavi Dhananjaya Mohan1, Shobith Rangappa2, S Chandra Nayak3
1Department of Studies in Molecular Biology, University of Mysore, Manasagangotri, Mysore, 570006, India.
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.
Insights
Natural products, especially bacterial metabolites, offer potent anticancer agents crucial for combating cancer mortality. Research highlights their diverse mechanisms and potential, alongside advancements in drug discovery through metagenomics.
Area of Science:
- Natural Products Chemistry
- Pharmacology
- Cancer Therapeutics
Background:
- Cancer is a leading global cause of mortality, with limited therapeutic options for many types, especially when diagnosed at advanced stages.
- Natural sources, particularly bacteria, are rich reservoirs of diverse compounds with significant pharmacological potential for drug development.
- Over 13,000 compounds from bacterial sources have been identified, highlighting their importance in medicinal chemistry.
Purpose of the Study:
- To review the significance of natural products, with a focus on bacterial metabolites, in the development of novel anticancer agents.
- To discuss the sources, mechanisms of action, toxicity, and off-target effects of clinically used bacterial-derived anticancer drugs.
- To explore promising secondary metabolites in clinical trials or preclinical development and the role of metagenomics in discovering new anticancer agents.
Main Methods:
- Comprehensive literature review of clinically used anticancer drugs derived from bacteria.
- Analysis of secondary metabolites with demonstrated anticancer activity in preclinical or clinical settings.
- Exploration of metagenomics as a tool for identifying novel anticancer compounds.
Main Results:
- Detailed discussion of established bacterial-derived anticancer drugs (e.g., actinomycin D, doxorubicin) including their therapeutic profiles and limitations.
- Overview of promising natural compounds (e.g., antimycins, salinosporamide) currently under investigation for cancer therapy.
- Identification of anticancer agents like bryostatin 1 and ET-743 discovered through metagenomic approaches.
Conclusions:
- Bacterial natural products represent a vital resource for developing effective anticancer therapies, addressing unmet clinical needs.
- Understanding the mechanisms, toxicities, and off-target effects of these agents is crucial for optimizing their clinical use.
- Metagenomics offers a powerful strategy for accelerating the discovery of novel, potent anticancer agents from diverse microbial communities.
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