Abstract
Purpose: To investigate the antiproliferative effect of the Red Sea cone snail, Conus geographus, against 4 MCF-7 (breast), MDA-MB-231 (epithelial human breast), HepG2 (hepatocellular) and SKOV-3 (ovarian) cancer cell lines.
 Methods: Extraction of Red Sea cone snail sample with a mixture of CH2Cl2 and CH3OH (1:1, v/v) yielded 0.55 g of a green viscous material. The cytotoxic effects of the organic extract against the cancer cell lines were determined using cell proliferation (MTT) assay, and the half-maximal concentration (IC50) values measured. The effect of the crude extract on the cell cycle of the HepG-2 was determined by flow cytometry.
 Results: The extract produced significant inhibitory effects against SKOV-3, MDA-MB-231, MCF-7 and HepG2, with IC50 values of 22.7 ± 2.2, 68.7 ± 6.2, 47 ± 4.2 and 19 ± 2.1 μg/mL, respectively. Cell cycle analysis revealed that the extract enhanced accumulation of HepG2 cells in the Go/G1 phase, at a level of 23.4 and 24.1 % at IC50 (19 μg/mL) and ½ IC50 (9.5 μg/mL), respectively, when compared to the untreated cells.
 Conclusion: These results indicate that C. geographus extract exhibits potent cytotoxic effect against HepG2 cells via a mechanism involving G0/G1 cell cycle arrest. Thus, C. geographus is a potential source of a new anti-cancer agent.
 Keywords: Conus geographus, Marine invertebrate, HepG2, Antiproliferation
Highlights
High biological diversity and harsh environmental conditions are the main features of marine ecosystems, and they reflect different archetypes of natural compounds, when compared to those originating from terrestrial organisms
The present study was carried out to investigate the cytotoxicity of the cone snail C. geographus from Saudi territorial waters against SKOV-3, MCF-7, MDA-MB-231 and HepG2 cancer cell lines
The results indicated that the C. geographus extract showed good antiproliferative activity against SKOV-3, MCF-7, MDA-MB-231 and HepG2 cell lines
Summary
High biological diversity and harsh environmental conditions are the main features of marine ecosystems, and they reflect different archetypes of natural compounds, when compared to those originating from terrestrial organisms. Several new compounds of marine origin are discovered every year [1, 2]. Many of these natural products have already been considered in clinical trials with regard to their antitumor activities. The present study was carried out to investigate the cytotoxicity of the cone snail C. geographus from Saudi territorial waters against SKOV-3, MCF-7, MDA-MB-231 and HepG2 cancer cell lines. HepG2 cells were treated with 9.5 and 19 μg/mL Conus extract, or with 0.5% DMSO as negative control. The fixed cells were washed with 1 x PBS and centrifuged at 5000 rpm for 15 min. Graphs were plotted using GraphPad Prism software, version 6.00 (GraphPad Software, La Jolla, CA)
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