Abstract
Prostate cancer (CaP) is one of the leading causes of death in men worldwide. Much attention has been given on its prevention and treatment strategies, including targeting the regulation of 5-alpha-Reductase (5αR) enzyme activity, aimed to limit the progression of CaP by inhibiting the conversion of potent androgen dihydrotestosterone from testosterone that is thought to play a role in pathogenesis of CaP, by using the 5-alpha-Reductase inhibitors (5αRis) such as finasteride and dutasteride. However, 5αRis are reported to exhibit numerous adverse side effects, for instance erectile dysfunction, ejaculatory dysfunction and loss of libido. This has led to a surge of interests on plant-derived alternatives that might offer favourable side effects and less toxic profiles. Phytochemicals from plants are shown to exhibit numerous medicinal properties in various studies targeting many major illnesses including CaP. Therefore, in this review, we aim to discuss on the use of phytochemicals namely phytosterols, polyphenols and fatty acids, found in various plants with proven anti-CaP properties, as an alternative herbal CaP medicines as well as to outline their inhibitory activities on 5αRs isozymes based on their structural similarities with current 5αRis as part of CaP treatment approaches.
Highlights
Prostate cancer (CaP) is the second most deadly malignancy in men after lung cancer and the fifth leading cause of death worldwide, accounting for 7.1% (1,276,106) of the new cases and 3.8% (358,989) of total death in males in 2018 (Rawla, 2019)
The results showed Oleic acid (OA) and linoleic acid (LNA) to be more potent against 5αR1 than 5αR2, while lauric acid (LA) was found to be potent against both 5αR1 and 5αR2, whereas, the inhibitory effect of myristic acid (MA) was found only active against type 2 and is a potent inhibitor of 5αR2
The androgens, which are the modulator of prostate growth, are thought to contribute to the pathogenesis of CaP and this has led to a surge of interest in studies that aim to block the activity of 5aRs, which are the enzymes responsible on converting androgen T to its potent form DHT, using available synthetic inhibitors of 5aRs resulting in androgens deprivation as part of the strategies
Summary
The authors should clarify the sentence “Testosterone (T), synthesised by the Leydig cells of the testes under the control of hypothalamus and anterior pituitary gland, is the most abundant circulating androgen in males, where from it, more potent form dihydrotestosterone (DHT) is synthesised”. The inclusion of this table would give important context on how these phytochemicals (i.e., PS, PP and FA) have been investigated in vivo and how much more work is needed. It would be helpful if the authors provided additional context in the discussion and included a sentence on how many (if any) of the phytochemicals (i.e., PS, PP and FA) have been investigated in human clinical trials to inhibit 5αRs, and what still needs to be done in future studies. Sheikh Naeem Shafqat, Universiti Brunei Darussalam, Jalan Tungku Link, Gadong, Brunei Reply to the comments made by the Reviewer (Dr Binesh Shrestha): Thank you for reviewing and suggesting some constructive amendments to the review article. Thank You, Regards, Dr Naeem Shafqat (Author of the article) Competing Interests: No competing interests were disclosed
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