Guineenoside B a triterpenoid saponin from Piper guineense (Piperaceae) triggers apoptosis and PI3K/Akt/mTOR inactivation and inhibits metastasis

Over 1.4 million new cases of prostate cancer (PCa) and 375,304 deaths were recorded in 2020. Piper guineense Schum and Thonn is used to treat various diseases including cancer. Three triterpenoid saponins namely guineenosides (Guin) A, B & C were recently isolated from this plant. This study marks the initial documentation of the anticancer potential of these compounds. Anti-cell growth (MTT), proliferation (CCK-8), clonogenic assays were evaluated. Furthermore, the most potent compound (Guin-B) was investigated for its potential to induce apoptosis, inhibit cell migration/invasion as well as cell adhesion. Some key proteins in cell proliferation and migration were evaluated. Out of the 3 saponins isolated from P. guineense, Guin-B exhibited significant and concentration-dependent inhibition of PC3 (IC50 =10 µg/mL or ~ 4.82 × 10− 6 µM) and LNCaP (IC50 = 8 µg/mL or 3.86 × 10− 6 µM) cell growth and proliferation as well as a potent inhibition (p < 0.001) of PC3 cell clone formation. Guin-B induced a potent (near 50%) increment of apoptotic cell population in PC3 and LNCaP cells at both 5 and 10 µg/mL; which was accompanied by a significant increase in caspase-3 activity. Guin-B induced a potent inhibition of PC3 cell migration and invasion and an increase in adherence of PC3 cells to the extracellular collagen and fibronectin matrix. A decrease in the expression of pAKT, AKT, mTOR and VEGF proteins was noticed following the treatment with Guin-B. Guineenosides B triggers apoptosis via mitochondrial pathway and PI3K/Akt/mTOR inactivation and inhibits metastasis at a low concentration, thus encouraging future investigation of this saponin.