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
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”.2
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
Summary
An in vitro metabolic study in hamster prostate by Marisa Cabeza and colleagues revealed that β-sitosterol inhibits the enzymatic activity of 5αRs in dose-dependent manner, which confirms the ability of β-sitosterol as a 5αRi (Cabezal et al, 2003) Another PS, stigmasterol, was reported to be associated with a reduction in common cancer risks including colon cancer, breast cancer and CaP (Bradford & Awad, 2007). Pais (2010) reported in his study that in a cell-free test system, ethanolic extract of Serenoa repens was a potent inhibitor of 5αR2 with 61% inhibition From these observations, β-sitosterol and stigmasterol are found to exhibit inhibitory activity on both isozymes of 5αRs. Various plants reported to have β-sitosterol as their major active compound include Hypoxis rooperi extract (Harzol®), Secale cereal (Rye Grass Pollen), Urtica dioica and Prunus Africana (Komakech et al, 2017; Madersbacher et al, 2007).
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