A thorough pharmacological evaluation of the new anticancer triterpenoid (nummularic acid) from Ipomoea batatas through in vitro, in silico and in vivo studies

Molecules. 2022 Apr 12;27(8):2474. doi: 10.3390/molecules27082474.

ABSTRACT

Prostate cancer (PCa) is the most common cancer in men, accounting for approximately 10% of all new cases in the United States. Plant-derived bioactive compounds, such as pentacyclic triterpenoids (PT), have the ability to inhibit PCa cell proliferation. We have isolated and characterized nummularic acid (NA), a potent PT, as a major chemical constituent of Ipomoea batatas, a medicinal food plant that has been used in ethnomedicine for centuries. In the current study, in vitro antiproliferative potential against PCa cells (DU145 and PC3) via the assay of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT ); Western blot protein expression analysis; absorption, distribution, metabolism, excretion (ADME); pharmacokinetic prediction studies; and bisphenol A (BPA)-induced prostate inhibition in Sprague Dawley rats were conducted to assess the anticancer capacity of NA. Important (p p 50 21.18 ± 3.43 µM against DU145 and 24.21 ± 3.38 µM against PC3 cells compared to cabazitaxel (9.56 ± 1.45 µM and 12.78 ± 2.67 µM) and doxorubicin controls (10.98 ± 2.71 µM and 15.97 ± 2.77 µM). Further in-depth mechanistic studies reveal that NA treatment significantly increased downstream caspase and PARP cleavage, up-regulated BAX and P53 and down-regulated BCL-2 and NF-.κB, inducing apoptosis in PCa cells. Pharmacokinetic and ADME characterization indicates that NA has a favorable physicochemical nature, with high gastrointestinal absorption, low blood-brain barrier permeability, no hepatotoxicity, and cytochrome inhibition. BPA-induced prostate gland disturbances in Sprague Dawley rats show a potential increase (0.478 ± 0.28 g) in prostate weight compared to control (0.385 ± 0.13 g). Multidose treatment with NA (10 mg/kg) significantly reduced prostate size (0.409 ± 0.21 g) compared to control. The NA-treated groups showed substantial restoration of hematological and histological parameters, recovery of serum hormones, and suppression of inflammatory markers. This multifaceted analysis suggests that NA, as a novel small molecule with a strong pharmacokinetic and pharmacological profile, has the potential to induce apoptosis and death in PCa cells.

PMID:35458672 | DO I:10.3390/molecules27082474