Phytochemical Analysis, Computational Modeling and Experimental Evaluations of Avicennia Marina Anti-cancer Activity on Breast, Ovarian and Cervical Cancer Cell Lines Running Title: Anti-cancer Activity of Avicennia Marina

Abstract

\n Background: Avicennia marina, the gray mangrove, is an herbal source of bioactive anti-cancer compounds.Purpose: The present study aimed to evaluate phytochemical compositions of ethanol and ethyl acetate extracts of A. marina leaves and experimental study and computational modeling of their anti-cancer activity on breast, ovarian and cervical cancer cell lines.Study design: Phytochemical analysis, computational modeling and experimental in vitro evaluationMethods: Phytochemical analysis and GC-MS analysis were used to detect phenolic and flavonoid contents in ethanol and ethyl acetate extracts of A. marina leaves. Cell proliferation, viability, cycle and western blot assays of the extracts were performed on MCF-7, OVCAR3, and HeLa. Computational modeling done to detect effective compounds.Results: The extracts of A. marina leaves had high phenolic and flavonoid contents. In GC-MS analysis of the extracts, anti-cancer and anti-proliferative compounds were detected. Moreover, after treatment of MCF-7, OVCAR3, and HeLa, separately, the MTT assay, cell proliferation assay, and cell viability assays showed anti-proliferative activity, decreasing of cell population and decreasing cell viability, respectively. In addition, the cell cycle analysis showed that the S phase of the cell cycle increased in MCF-7. Moreover, the western blot analysis showed that the pro-apoptotic cell effectors such as Bax and caspase-1, -3, and -7 increased. Computational results of affinity of ligands detected by GC-MS compounds and stimulated apoptosis effectors detected by western blot showed five molecules in A. marina leaves playing role in OVCAR3 and HeLa apoptosis.Conclusion: The extracts of A. marina leaves have anti-cancer effects on breast, ovarian and cervical cancer cells via cell cycle arrest or apoptotic mechanisms.