~ 232 ~ Journal of Pharmacognosy and Phytochemistry 2019; 8(2): 232-237 E-ISSN: 2278-4136 P-ISSN: 2349-8234 JPP 2019; 8(2): 232-237 Received: 03-12-2018 Accepted: 27-02-2019 Debby Desmarini Master Student of Biomedical Science Program, Faculty of Medicine, Universitas Indonesia Murdani Abdullah Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia Puji Sari Department of Biology Medicine, Faculty of Medicine, Universitas Indonesia Luluk Yunaini Department of Biology Medicine, Faculty of Medicine, Universitas Indonesia Fadilah Fadilah Department of Medical Chemistry, Faculty of Medicine, University of Indonesia Correspondence Murdani Abdullah Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia Effects of ethanolic leave extract of soursop ( Annona muricata L.) on human colorectal cancer line: cell viability and in silico study to cyclin d1 protein Debby Desmarini, Murdani Abdullah, Puji Sari, Luluk Yunaini and Fadilah Fadilah 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 the high proliferation of colorectal cell. Treatment and prevention of colorectal cancer could be done naturally by consuming leave extract of Annona muricata L. (soursop). Soursop is known for many phytochemical components such as alkaloid, annonaceous acetogenin, phenol, and flavonol that serve as an anti-cancer. Method: The research was used HT-29 colorectal cell that given ethanolic leave extract of soursop with 278 μg/mL concentration, 5-Fluorourasil (5-FU) with 88 μg/mL concentration as positive control, solvent control, dan cells control as negative control. The parameters are cell viability with MTT Assay and analysis of molecular docking from ethanolic leave extract of soursop to cyclin D1 protein with molecular operating environment (MOE) 2013.08 software. Result: Percentage of viable HT-29 cell line decrease in accordance with increasing concentration and the lowest percentage of viable cell is 2 x cytotoxicity concentration 50 (CC50) after ethanolic leave extract of soursop treatment (40,4±1,3%) was compared to 5-FU (30,68±0,93%), 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 that have the lowest free energy (ΔG), i.e 9,7755 kkal/mol and -7,2147 kkal/mol. Conclusion: Ethanolic leave extract of soursop causes decreasing cell viability of HT-29 cell line on 2 x CC50 concentration was compared to 5-FU, solvent control, dan cells control. N-hexadecanoic acid and phytol molecules have ability to inhibit cyclin D1 protein. Keywords: Colorectal cancer, ethanolic leave extract of soursop, cell proliferation, molecular docking, cyclin D1 Introduction Colorectal cancer is a pathological changes in normal colon and rectal tissue to an abnormal tissue caused by genetic and environmental changes [1] . According to International Agency for Research on Cancer (IARC), the colorectal cancer incidence of men in the world is the third largest case (21%) after lung cancer and prostate cancer, while the colorectal cancer incidence of women in the world is the second largest case (14%) after breast cancer [2] . The therapy of colorectal cancer are used to surgery, radiotherapy and chemotherapy [3] . These are less effective because of side effects so the alternative therapy are needed, such as consuming Annona muricata L. (soursop) [4, 5] . Annona muricata L. is a type of tropical plant known for containing many phytochemical components such as alkaloids, annonaceous acetogenin, megastigman, flavonol triglycosides, phenolics, and cyclopeptides and the find at the leaves, fruits, seeds, and roots that can act as anti-inflammatory, anti-inflammatory infection and anti-cancer [6, 7] . Soursop leave extract can produce cytotoxic effects on colorectal cancer cell cultures such as HT-29, HCT-116, [5] COLO-205, [8] and DLD-1 [9] . Soursop leave extract is also known to reduce the expression of cyclin D1 protein in phase G1/S [5, 10] . Cyclin D1 is a protein encoded by CCND1 gene and controls cell cycle especially at the G1 phase. In this process, the expression of cyclin D1 protein increases and binds to cyclin dependent kinase 4 or 6 (CDK4/6) protein to form active kinase. That complex can phosphorylate or inactivate the retinoblastoma (Rb) protein. The phosphorylated Rb causes a transcription factor E2 factor (E2F) to promote the transcription of genes that needed for cell division [11] .