ANDROGEN LEVELS IN NIGERIAN PROSTATE CANCER PATIENTS AND IN SILICO SCREENING OF POTENTIAL INHIBITORS OF SRD5A2 ENZYME
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Globally, cancer has been recognized as the second most common disease occurring in various
organs of the body. Prostate cancer (PC) is among the most prevalent cancer types. It is
reportedly the most common form of male cancer in men of African descent, having the highest
susceptibility rate. Androgens, such as testosterone and dihydrotestosterone (DHT), are among
several risk factors associated with PC risk and progression. They have been well-established
to have an essential role in PC development, even at advanced stages. Dihydrotestosterone
(DHT), a more active androgen, has been linked to PC development and progression due to its
ability to bind the androgen receptor (AR) and initiate its signalling. The steroid 5-alphareductase
type-2 (SRD5A2) enzyme, which transforms testosterone into DHT, has been
targeted in hormonal therapy for PC using finasteride. However, side effects, including sexual
dysfunction, osteoporosis, and cardiovascular diseases, have been associated with the
treatment, thereby indicating a need for novel and safer SRD5A2 inhibitors. This study was
aimed at determining the levels of circulating androgens (Testosterone and DHT) among
Nigerian prostate cancer patients and identify potential drug targets against these androgens.
Testosterone and DHT levels were determined using an ELISA assay. A systematic review was
performed to identify previously reported plants as SRD5A2 inhibitors, including their
phytoconstituents. Thirty-four phytoconstituents from nine medicinal plants were selected and
evaluated alongside the standard SRD5A2 inhibitor (finasteride) by employing in silico
techniques, including molecular docking, pharmacokinetic prediction, and toxicity profiling.
Among the bioactive compounds evaluated, gamma-oryzanol showed the highest binding
affinity with SRD5A2 with a binding energy of -11.6 Kcal/mol comparable to the finasteride.
Its pharmacokinetics and toxicity profiles were also predicted to be better than finasteride,
suggesting its therapeutic potential in drug development for PC treatment. However, further
studies should be conducted on gamma-oryzanol to ascertain its toxicity compared to
finasteride. We also recommend that additional studies be carried out to evaluate the expression
of the SRD5A2 gene in Nigerian PC patients, as this would help establish a personalized
treatment for this population.
Keywords
QD Chemistry, QH301 Biology, RA0421 Public health. Hygiene. Preventive Medicine