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Manzamine A: A promising marine-derived cancer therapeutic for multi-targeted interactions with E2F8, SIX1, AR, GSK-3β, and V-ATPase - A systematic review

Mishan MA 1 , Choo YM 2 , Winkler J 3 , Hamann MT 4 , Karan D 5

Affiliations 

  • 1 Department of Urology, Brown Cancer Center, 505 S Hancock Street, Louisville, KY, USA
  • 2 Department of Chemistry, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia
  • 3 Department of Chemistry, The University of Pennsylvania, Philadelphia, PA, USA
  • 4 Department of Drug Discovery and Biomedical Sciences and Public Health, Colleges of Pharmacy and Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA
  • 5 Department of Urology, Brown Cancer Center, 505 S Hancock Street, Louisville, KY, USA. Electronic address: dev.karan@louisville.edu
Eur J Pharmacol, 2025 Mar 05;990:177295.
PMID: 39863145 DOI: 10.1016/j.ejphar.2025.177295

Abstract

Manzamine A, a natural compound derived from various sponge genera, features a β-carboline structure and exhibits a range of biological activities, including anti-inflammatory and antimalarial effects. Its potential as an anticancer agent has been explored in several tumor models, both in vitro and in vivo, showing effects through mechanisms such as cytotoxicity, regulation of the cell cycle, inhibition of cell migration, epithelial-to-mesenchymal transition (EMT), autophagy, and apoptosis through multi-target interactions of E2F transcriptional factors, ribosomal S6 kinases, androgen receptor (AR), SIX1, GSK-3β, v-ATPase, and p53/p21/p27 cascades. This systematic review evaluates existing literature on the potential application of this marine alkaloid as a novel cancer therapy, highlighting its promising ability to inhibit cancer cell growth while causing minimal side effects.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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