Carica papaya (papaya) has been traditionally used to treat various diseases including cancer. Recent report suggested that Carica papaya leaf extract (CPE) have anticancer activity.
However its mode of action remains unexplored. The aim of the present study is to evaluate its effect on mitochondrial fusion and associated mechanisms for induction of apoptosis in prostate carcinoma cell lines (PCa).CPE treatment at concentration (5, 10, 25µl/ml) for 24 hrs and 48 hrs decrease the cell proliferation and induce the G1 and both G1, G2/M phase of cell cycle arrest in LNCaP and PC-3 cells. The cell cycle arrest associated with induction of mitochondria mediated apoptosis in prostate cancer cells. Induction of apoptosis is accompanied by the depolarization of mitochondrial membrane potential, an increase in the expression level of Bax protein and enhanced cleavage of Poly(ADP-ribose) polymerase.
In addition Dynamin-related protein1 (Drp1), a member of the dynamin family of GTPases required for mitochondrial fission has been found up regulated in certain types of cancer. CPE treatment reduces mitochondrial fission and induces mitochondrial fusion by down regulate the level of Drp1protein.Activation of Drp1 required B1/ Cyclin-dependent kinase 1(cdk1)which helps to phosphorylation of Drp1 at ser 616 causing mitochondrial fission. CPE treatment down regulates the expression of B1/cdk complexes in prostate cancer cell line (PC-3). These findings suggest that CPE targetingDrp1- mediated mitochondrial fission and fusions can effective therapy for prevention of prostate cancer.