The Effect of Graviola Leaves Extract on the Progression of Pancreatic Cancer in Rats

Abstract

Pancreatic tumor is a lethal malignancy resistant to conventional current protocols for management including surgical intervention, chemotherapy, and radiation which possesses adverse effects. The present study was designed to evaluate the effects of an extract from Annona Muricata, known as Graviola. Graviola leaves extract (GLE) contain bioactive compound "annonaceous acetogenins" known for anticancer activity on cancer cell lines. This study aimed to explore the molecular mechanisms involved in the progression of pancreatic cancer PC including: redox status, oxidative stress, gene and microRNA expression, and the protective and therapeutic effect of GLE against PC. The study was divided into two phases of male Sprague Dawley rats; to study the protective effect of GLE in one using DMBA for (PC) induction, and GLE effect as adjuvant therapy, blood and pancreatic tissue samples were obtained for assessment of different parameters. These parameters indicated impaired liver and kidney functions in the positive control group (Group II) compared to control (Group I) and co-treated groups (Group III), while in phase II no changes were found, except in treated groups. Also lipid peroxidation, antioxidant capacity, levels of inflammatory cytokines, and expression of NF-κB, COX-2, VEGF-A, iNOS, TNF-α and miRNA levels (miRNA 21, 34a, and 200b) showed aberrant expression in positive control group compared to other groups in both phases. Our findings suggest that microRNAs imbalance in miRNA-21, miRNA-34a and miRNA-200b could be exploited as novel biomarkers for diagnostic and prognostic assessments of PC and as targets for therapy. Collectively, GLE showed significant cytotoxic activity against pancreatic carcinogenesis through multiple pathways motensive nonpregnant women; thereby, exposing them to cardiovascular risks in the near future.