The effect of ethanolic leaves extract of soursop (Annona muricata L.) on human colorectal cancer cell line: cell viability and in silico study to cyclin D1 protein

Abstract

Introduction: Colorectal cancer is a pathological transformation of normal colon and rectum epithelial that becomes an abnormal tissue mass, due to the overexpression of cyclin D1 protein that inducing excessive proliferation of colorectal cell. The treatment and prevention of colorectal cancer could be done naturally by consuming leaves extract of Annona muricata L. (soursop). Soursop is known for many phytochemical components that serve as an anti-cancer. Methods: This study was used HT-29 colorectal cancer cell that treated with ethanolic leaves extract of soursop and 5-Fluorourasil (5-FU) to find the cytotoxicity concentration that can inhibit 50% of HT-29 cell population (CC50) and the next concentrations of them were treated for next treatment with MTT assay. Molecular docking analysis of the compounds of ethanolic leaves extract of soursop to cyclin D1 protein used molecular operating environment (MOE) 2013.08 software. Results: CC50 of ethanolic leaves extracts of soursop was 278 μg/mL dan 5-FU was 88 μg/mL. The lowest percentage of viable HT-29 cell was 2 x CC50 after ethanolic leaves extract of soursop treatment (40,4±1,3%) was compared to 5-FU (52,8±4,3%), solvent control (97,2±1,4%), and cells control (100%). Analysis of molecular docking to cyclin D1 protein was obtained N-hexadecanoic acid and phytol molecules as good candidates to inhibit cyclin D1 protein. Conclusions: The ethanolic leaves extract of soursop could be a good alternative treatment for colorectal cancer and its compounds had ability to inhibit cyclin D1 protein (the highest gibbs free energy (ΔG) and affinity (pKi)). (Health Science Journal of Indonesia 2019;10(2):96-102)