Abstract

The initial responses to standard chemotherapies among prostate cancer (PCa) patients are usually significant, while most of them will finally develop drug resistance, rendering them with limited therapies. To discover new regimens for the treatment of PCa including resistant PCa, natural products, the richest source of bioactive compounds, can serve as a library for screening and identifying promising candidates, and flavones such as apigenin and genistein have been used in lab and clinical trials for treating PCa over decades. In this mini-review, we take a look into the progress of apigenin and genistein, which are isomers, in treating PCa in the past decade. While possessing very similar structure, these two isomers can both target the same signaling pathways; they also are found to work differently in PCa cells. Given that more combinations are being developed and tested, genistein appears to be the more promising option to be approved. The anticancer efficacies of these two flavones can be confirmed by in-vitro and in-vivo studies, and their applications remain to be validated in clinical trials. Information gained in this work may provide important information for new drug development and the potential application of apigenin and genistein in treating PCa.

Highlights

  • Prostate cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer death in men

  • The above information strongly supports the potential application of apigenin and genistein in treating PCa including resistant forms

  • There will be an estimate of 248,530 cases

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Summary

INTRODUCTION

Prostate cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer death in men (do Pazo and Webster, 2021; Whitaker et al, 2020; Komura et al, 2018; Dunn, 2017). In-vivo studies of xenograft mouse model indicate that apigenin (20 and 50 μg/day, gavage) suppressed tumor growth, lowered cancer cells proliferation, and enhanced apoptosis, mediated with the inhibition of p-IKKα, NF-κB/p65 (Shukla et al, 2015). A similar study by the same group (2016) showed that apigenin (0–100 μM) inhibited CSCs (CD44+ PCa stem cells) and PC-3 cell survival, with a significant increase of p21 and p27, both of which are anti-apoptotic proteins It appeared that apigenin induced apoptosis via an extrinsic caspase-dependent pathway mediated by up-regulating the mRNA expressions of caspases-8, -3, and TNF-α, but failed to trigger the intrinsic pathway as determined by the levels of pro-apoptotic Bax, cytochrome C, and Apaf-1 in CSCs. While in contrast in PC-3 cells, apigenin exerted cytotoxic effects via intrinsic apoptosis pathway.

SUMMARY AND BRIEF DISCUSSION
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