Anticancer effect of docetaxel induces apoptosis of prostate cancer via the cofilin-1 and paxillin signaling pathway

Abstract

Prostate cancer is a common multiple malignant tumor occurring in males. Prostate cancer mortality is the 2nd most common of all tumor types in Western countries and the mortality of morbidity is 13% in the USA. The present study aimed to investigate the anticancer effect of docetaxel on inducing the apoptosis of prostate cancer via the cofilin‑1 and paxillin signaling pathway. Treatment with docetaxel (1‑50 nM) disposed the human LNCaP prostate cancer cells for 24 h. Cell growth and cytotoxicity were subsequently measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and lactate dehydrogenase assay, respectively. Docetaxel-induced cell death was analyzed using flow cytometric and caspase-3 assays. Reverse transcription‑quantitative polymerase chain reaction analysis was used to detect the gene expression of cofilin‑1 and western blots were used to determine the protein expression of paxillin. Treatment with docetaxel inhibited cell growth, promoted cytotoxicity, activated apoptosis and increased caspase‑3 activity in the LNCaP cells. Notably, administration of docetaxel reduced the gene expression of cofilin‑1 and the protein expression of paxillin in the LNCaP cells. Additionally, knockdown of cofilin‑1 advanced the anticancer effect of docetaxel against LNCaP cells through suppression of the paxillin pathway. The present findings demonstrated that the anticancer effect of docetaxel induces the apoptosis of prostate cancer via the suppression of the cofilin‑1 and paxillin signaling pathways, which will assist in setting a stage for the clinical treatment of prostate cancer.

Cofilin-1 and Other ADF/Cofilin Superfamily Members in Human Malignant Cells

“…Cfl-1 can be a target for chemotherapeutic treatment. It has been shown that docetaxel induces the apoptosis of prostate cancer cells via suppression of the cofilin signaling pathways [ 157 ]. The increased level of Cfl-1 in HMCs is often associated with poor prognosis which can be related with cofilin-dependent drug resistance of cancer cells [ 142 , 150 , 158 ].…”

Combinatorial effect of curcumin with docetaxel modulates apoptotic and cell survival molecules in prostate cancer

“…Treatment of PCa with docetaxel inhibits proliferation and activates apoptosis, however, promotes cytotoxicity in PCa (6–8). Thus, patients receive prolonged treatment with docetaxel experience a transient benefit but develop incurable drug resistance and cytotoxicity (9).…”

Changes in Vasodilator-Stimulated Phosphoprotein Phosphorylation, Profilin-1, and Cofilin-1 in Accreta and Protection by DHA

“…Evidence from cancer studies associates cofilin-1 with increased proliferation and reduced apoptosis. [56][57][58] Significantly induced expression of proapoptotic caspase-9 and suppression of antiapoptotic BCL-2, with cofilin-1 trending lower, suggest DHA-modulating effects similar to cofilin-1 knockdown in bladder cancer cells 56 and suggests that reduced BeWo cell growth was at least partially due to increased apoptosis. Because accreta tissue are characterized by increased trophoblast proliferation regardless of severity, 11 inducing apoptosis in overproliferative trophoblasts may have therapeutic benefit.…”