Antiproliferative and Anti‑invasion Effects of Carvacrol on PC3 Human Prostate Cancer Cells through Reducing pSTAT3, pAKT, and pERK1/2 Signaling Proteins

Abstract

Background: One of the most effective parameters in the progression of the prostate cancer is interleukin (IL)‑6 through affecting pSTAT3, pERK1/2, and pAKT cell signaling proteins. Carvacrol is an herbal antioxidant with antitumor effects. The purpose of this study was to investigate the effects of carvacrol on IL‑6 gene expression, pSTAT3, pAKT, pERK1/2 cellular signaling proteins, and invasion in human prostate cancer PC3 cells.

Methods: PC3 cell viability was evaluated by MTT assay with different concentrations of carvacrol (0–800 µM). IL‑6 gene expression and cellular concentration of pSTAT3, pERK1/2, and pAKT were investigated using the real‑time reverse transcription quantitative polymerase chain reaction (RT‑qPCR) and western blotting technic, respectively. PC3 cell invasion was determined by invasion assay test.

Results: Carvacrol IC 50 for PC3 prostate cancer cells was 360 µM. Carvacrol led to a significant reduction (P < 0.05) for IL‑6 gene expression in a dose‑dependent manner compared to control. IL‑6 protein reduced 41.5% and 52.7% when compared with control cells at 360 and 420 µM of carvacrol, respectively.
Carvacrol led to a decline in pSTAT3, pAKT, and pERK1/2 above 360 µM compared to control. PC3 potential invasion was significantly reduced after treatment with carvacrol in a dose‑dependent manner.

Conclusions: Decreased IL‑6 protein level by carvacrol resulted in diminishing of pSTAT3, pERK1/2, and pAKT signaling proteins, which leads to the reduction of the cell survival, proliferation, and invasion in PC3 cells.

Keywords: Cell survival, interleukin‑6, prostatic neoplasms, STAT3 protein, terpenes