Silver Nanoparticles Synthesized Using Carica papaya Leaf Extract (AgNPs-PLE) Causes Cell Cycle Arrest and Apoptosis in Human Prostate (DU145) Cancer Cells

Abstract

Treatment of cancer has been limited by the poor efficacy and toxicity profiles of available drugs. There is a growing demand to develop alternative approaches to combat cancer such as use of nano-formulation-based drugs. Here, we report biosynthesis and characterization of silver nanoparticles (AgNPs) with papaya leaf extract (PLE) and its anti-cancer properties against different human cancer cells. Purified nanoparticles were characterized by standard techniques, such as TEM, STM, SEM, EDS, XRD, and FTIR. Furthermore, cytotoxic activity of AgNPs-PLE was carried out against different human cancer cells and non-tumorigenic human keratinocytes cells. AgNPs-PLE when compared with AgNPs-citric acid or PLE showed better efficacy against cancer cells and was also relatively less toxic to normal cells. Treatment of DU145 cells with AgNPs-PLE (0.5-5.0 μg/ml) for 24-48 h lowered total cell number by 24-36% (P < 0.05). Inhibition of cell growth was linked with arrest of cell cycle at G2/M phase at 24 h, while G1 and G2/M phase arrests at 48 h. ROS production was observed at earlier time points in presence of AgNPs-PLE, suggesting its role behind apoptosis in DU145 cells. Induction of apoptosis (57%) was revealed by AO/EB staining in DU145 cells along with induction of Bax, cleaved caspase-3, and cleaved PARP proteins. G1-S phase cell cycle check point marker, cyclin D1 was down-regulated along with an increase in cip1/p21 and kip1/p27 tumor suppressor proteins by AgNPs-PLE. These findings suggest the anti-cancer properties of AgNPs-PLE.

Keywords: Anticancer; Apoptosis; Carica papaya leaf extracts; Prostate cancer; Silver nanoparticles.