The potential roles of gossypol as anticancer agent: advances and future directions

Danijela Paunovic; Jovana Rajkovic; Radmila Novakovic; Jelica Grujic-Milanovic; Reham Hassan Mekky; Dragos Popa; Daniela Calina; Javad Sharifi-Rad

doi:10.1186/s13020-023-00869-8

The potential roles of gossypol as anticancer agent: advances and future directions

Chin Med. 2023 Dec 15;18(1):163. doi: 10.1186/s13020-023-00869-8.

Authors

Danijela Paunovic¹, Jovana Rajkovic², Radmila Novakovic³, Jelica Grujic-Milanovic⁴, Reham Hassan Mekky⁵, Dragos Popa⁶, Daniela Calina⁷, Javad Sharifi-Rad⁸

Affiliations

¹ Institute for Biological Research Sinisa Stankovic, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia.
² Institute for Pharmacology, Clinical Pharmacology and Toxicology, Medical Faculty, University of Belgrade, Belgrade, Serbia.
³ Center for Genome Sequencing and Bioinformatics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11042, Belgrade, Serbia.
⁴ Institute for Medical Research, National Institute of the Republic of Serbia, Department for Cardiovascular Research, University of Belgrade, Belgrade, Serbia.
⁵ Department of Pharmacognosy, Faculty of Pharmacy, Egyptian Russian University, Badr City, 11829, Cairo, Egypt. reham-mekky@eru.edu.eg.
⁶ Department of Plastic Surgery, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania.
⁷ Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania. calinadaniela@gmail.com.
⁸ Facultad de Medicina, Universidad del Azuay, Cuenca, Ecuador. javad.sharifirad@gmail.com.

Abstract

Gossypol, a polyphenolic aldehyde derived from cottonseed plants, has seen a transformation in its pharmaceutical application from a male contraceptive to a candidate for cancer therapy. This shift is supported by its recognized antitumor properties, which have prompted its investigation in the treatment of various cancers and related inflammatory conditions. This review synthesizes the current understanding of gossypol as an anticancer agent, focusing on its pharmacological mechanisms, strategies to enhance its clinical efficacy, and the status of ongoing clinical evaluations.The methodological approach to this review involved a systematic search across several scientific databases including the National Center for Biotechnology Information (NCBI), PubMed/MedLine, Google Scholar, Scopus, and TRIP. Studies were meticulously chosen to cover various aspects of gossypol, from its chemical structure and natural sources to its pharmacokinetics and confirmed anticancer efficacy. Specific MeSH terms and keywords related to gossypol's antineoplastic applications guided the search strategy.Results from selected pharmacological studies indicate that gossypol inhibits the Bcl-2 family of anti-apoptotic proteins, promoting apoptosis in tumor cells. Clinical trials, particularly phase I and II, reveal gossypol's promise as an anticancer agent, demonstrating efficacy and manageable toxicity profiles. The review identifies the development of gossypol derivatives and novel carriers as avenues to enhance therapeutic outcomes and mitigate adverse effects.Conclusively, gossypol represents a promising anticancer agent with considerable therapeutic potential. However, further research is needed to refine gossypol-based therapies, explore combination treatments, and verify their effectiveness across cancer types. The ongoing clinical trials continue to support its potential, suggesting a future where gossypol could play a significant role in cancer treatment protocols.

Keywords: Anticancer mechanisms; Apoptosis; Gossypol; Mechanisms; Molecular targets; Proliferation.

Publication types

Review