Carica papaya (papaya), from the family of Caricaceae, is a perennial plant originating from the Southern part of Mexico. Carica papaya leaf extract (CPE) has been traditionally used to treat various diseases, including infectious diseases and cancer. However, the anticancer effects and molecular mechanism of CPE are elusive. The aim of our study is to examine the anticancer effects of aqueous leaf extract of Carica papaya against prostate cancer (PCa). We investigated the effect of CPE on LNCaP, DU145 and PC-3 PCa cells. CPE treatment (5, 10, 25µl/ml) significantly reduced the cell proliferation and induced cell death in PCa cells. Furthermore, we found that CPE induced G1, S and G1 as well as G2/M phase cell cycle arrest in LNCaP, DU145, and PC-3 cells, respectively. At molecular level, the cell cycle arrest was associated with decreased expression of CDK 4, cyclin D1, cyclin B1, and PCNA. CPE induced cell death was associatedwith depolarization of mitochondrial membrane potential, increase in ratio of Bax/Bcl2, cleavage of caspase-3 and cleaved -Poly(ADP-ribose) polymerase (PARP). CPE treatment also reduced mitochondrial fission and induced mitochondrial fusion by reducing the level of Drp1 protein. Further, we observed that CPE increased the expression of E-cadherin and decreased the expression of N-cadherin and vimentin. We checked the CPE toxicity in C57BL/6 male mice. We found that oral administration of CPE(0.25%, 0.5% and 1% v/v) in drinking water did not show any significant changes in body weight, water consumption and food intake as compared to control group. Collectively, CPE inhibited cell proliferation, induced cell death via apoptosis, mitochondrial fusion, epithelial marker and reduced mesenchymal markers.In vivo toxicity study with CPE treatment via drinking water was found to be non-toxic. These findings suggest that CPE has potential as anticancer therapeutic option for prevention and treatment of prostate cancer.
Citation Format: Surya Pratap Singh, Sivapar V. Mathan, Arpit Dheeraj, Dhanir Tailor, Rana P. Singh, Arbind Acharya. Anticancer effects and associated molecular changes of Carica papaya against prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3004.