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Review

The Role of Natural Chalcones and Their Derivatives in Targeting Prostate Cancer: Recent Updates

by
Ola J. Hussein
1,
Dana Elkhalifa
2,3,
Arij Fouzat Hassan
1,
Feras Alali
1,*,
Ala-Eddin Al Moustafa
4,5,6 and
Ashraf Khalil
7
1
Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar
2
Department of Pharmacy, Aspetar Orthopedic and Sports Medicine Hospital, Doha P.O. Box 29222, Qatar
3
College of Health and Life Sciences, Hamad Bin Khalifa University, Doha P.O. Box 34110, Qatar
4
College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar
5
Oncology Department, Faculty of Medicine, McGill University, Montreal, QC H3G 2M1, Canada
6
ABS Research Review & Consultation, Montreal, QC H4L 4P8, Canada
7
College of Pharmacy, Dubai Medical University, Dubai 19099, United Arab Emirates
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(24), 12082; https://doi.org/10.3390/ijms262412082
Submission received: 12 November 2025 / Revised: 9 December 2025 / Accepted: 12 December 2025 / Published: 16 December 2025
(This article belongs to the Special Issue Drug Discovery Based on Natural Products)
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Abstract

Prostate cancer (PCa) is the second most prevalent cancer among men and a major cause of cancer-related mortality worldwide. Despite an initial favorable response to hormone-based therapies, many patients ultimately develop an advanced and lethal form of the disease, referred to as castration-resistant PCa (CRPC). CRPC is associated with poor prognosis and a lack of effective curative treatments. As a result, new alternatives or improved therapeutic strategies to combat this life-threatening condition are urgently needed. Chalcones, also referred to as 1,3-diphenyl-2-propen-1-ones, have attracted significant attention because of their potent antitumor properties. Owing to their distinctive chemical structure and diverse biological activities, these compounds are promising candidates for treating various cancers, including PCa. Both naturally occurring and synthetically derived chalcones have demonstrated anticancer potential by modulating key cellular processes, including apoptosis, cell cycle regulation, cell migration, invasion, metastasis and angiogenesis, as well as major signaling pathways, such as PI3K/Akt/mTOR, androgen signaling, and NF-κB. This review aims to outline the recent advances in the therapeutic potential of chalcone derivatives in prostate cancer, with a focus on their molecular targets, mechanisms of action, and translational relevance.
Keywords: chalcone; prostate cancer; antitumor activities; metastasis; therapy chalcone; prostate cancer; antitumor activities; metastasis; therapy
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MDPI and ACS Style

Hussein, O.J.; Elkhalifa, D.; Hassan, A.F.; Alali, F.; Al Moustafa, A.-E.; Khalil, A. The Role of Natural Chalcones and Their Derivatives in Targeting Prostate Cancer: Recent Updates. Int. J. Mol. Sci. 2025, 26, 12082. https://doi.org/10.3390/ijms262412082

AMA Style

Hussein OJ, Elkhalifa D, Hassan AF, Alali F, Al Moustafa A-E, Khalil A. The Role of Natural Chalcones and Their Derivatives in Targeting Prostate Cancer: Recent Updates. International Journal of Molecular Sciences. 2025; 26(24):12082. https://doi.org/10.3390/ijms262412082

Chicago/Turabian Style

Hussein, Ola J., Dana Elkhalifa, Arij Fouzat Hassan, Feras Alali, Ala-Eddin Al Moustafa, and Ashraf Khalil. 2025. "The Role of Natural Chalcones and Their Derivatives in Targeting Prostate Cancer: Recent Updates" International Journal of Molecular Sciences 26, no. 24: 12082. https://doi.org/10.3390/ijms262412082

APA Style

Hussein, O. J., Elkhalifa, D., Hassan, A. F., Alali, F., Al Moustafa, A.-E., & Khalil, A. (2025). The Role of Natural Chalcones and Their Derivatives in Targeting Prostate Cancer: Recent Updates. International Journal of Molecular Sciences, 26(24), 12082. https://doi.org/10.3390/ijms262412082

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