Fatemeh Heidary Jamebozorgi1,2, Morteza Yousefzadi1, Omidreza Firuzi2, Meliika Nazemi3, Amir Reza Jassbi4. 1. Department of Marine Biology, Faculty of Marine Sciences and Technology, University of Hormozgan, Bandar Abbas, Iran. 2. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Zip: 71348-53734, Iran. 3. Persian Gulf and Oman Sea Ecological Research, Agricultural Research, Education and Extension Organization, Iranian Fisheries Research Institute, Bandar Abbas, Iran. 4. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Zip: 71348-53734, Iran. jassbiar@sums.ac.ir.
Abstract
PURPOSE: Marine sponges are rich sources of anticancer metabolites. Axinella sinoxea is a less studied sponge, found in the Larak Island's waters, of the Persian Gulf. In the present study, we have explored the cytotoxic properties and chemical constituents of A. sinoxea. METHODS: Repeated silica gel flash column chromatography of methanol extract of the Axinella sinoxea sponge, yielded fatty acid and sterol fractions. These fractions were analyzed by GC-MS and their anti-proliferative activities were evaluated by MTT assay against three human cancer cell lines including MOLT-4, MCF-7 and HT-29 as well as NIH/3 T3 fibroblast cells. The sterol-rich fractions were pooled and purified by HPLC and its sub fractions' cytotoxic activities were evaluated by MTT assay against MOLT-4 and NIH/3 T3 cells. RESULTS: The GC-MS spectral analysis of a fraction eluted with hexane: diethyl ether (90: 10), resulted in the identification of twelve fatty acids, including five linear chain saturated fatty acids; tetrdecanoic acid (1), pentadecanoic acid (3), hexadecanoic acid (5), heptadecanoic acid (7), and octadecanoic acid (10); one branched chain isoprenoid fatty acid, 4,8,12-trimethyltridecanoic acid (2); four monoenoic fatty acids; 9-hexadecenoic acid (4), 7-methyl-6-hexadecanoic acid (6), 9-octadecenoic acid (8) and 11-octadecenoic acid (9) and two polyunsaturated fatty acids; 5,8,11,14-eicosatetraenoic acid (11) and 4,7,10,13,16,19-docosahexaenoic acid (12). Spectral analysis of a non-polar fraction eluted with hexane: diethyl ether (85: 15), resulted in the identification of eight steroids including: cholesta-5,22-dien-3β-ol (13), cholest-5-en-3β-ol (14), ergosta-5,22-dien-3β-ol (15), ergost-5-en-3β-ol (16), stigmasta-5,22-dien-3β-ol (17), γ-sitosterol (18), 33-norgorgosta-5,24(28)-dien-3β-ol (19) and stigmasta-5,24(28)-dien-3β-ol (20). Fatty acids-containing fraction was active against HT-29 cell line with IC50 26.52 ± 8.19 μg/mL, while the steroids-rich fraction was active against the three above mentioned cell lines with IC50 values of 1.20 ± 0.24, 4.12 ± 0.40 and 2.47 ± 0.31 μg/mL, respectively. All of the above-mentioned fractions and sub-fractions were inactive (IC50s > 50 μg/mL) when assayed against normal fibroblast cells. CONCLUSION: The present study suggests A. sinoxea as a potential natural source of cancer chemotherapeutics. Graphical abstract Cytotxic constituents of Axinella sinoxea.
PURPOSE: Marine sponges are rich sources of anticancer metabolites. Axinella sinoxea is a less studied sponge, found in the Larak Island's waters, of the Persian Gulf. In the present study, we have explored the cytotoxic properties and chemical constituents of A. sinoxea. METHODS: Repeated silica gel flash column chromatography of methanol extract of the Axinella sinoxea sponge, yielded fatty acid and sterol fractions. These fractions were analyzed by GC-MS and their anti-proliferative activities were evaluated by MTT assay against three humancancer cell lines including MOLT-4, MCF-7 and HT-29 as well as NIH/3 T3 fibroblast cells. The sterol-rich fractions were pooled and purified by HPLC and its sub fractions' cytotoxic activities were evaluated by MTT assay against MOLT-4 and NIH/3 T3 cells. RESULTS: The GC-MS spectral analysis of a fraction eluted with hexane: diethyl ether (90: 10), resulted in the identification of twelve fatty acids, including five linear chain saturated fatty acids; tetrdecanoic acid (1), pentadecanoic acid (3), hexadecanoic acid (5), heptadecanoic acid (7), and octadecanoic acid (10); one branched chain isoprenoid fatty acid, 4,8,12-trimethyltridecanoic acid (2); four monoenoic fatty acids; 9-hexadecenoic acid (4), 7-methyl-6-hexadecanoic acid (6), 9-octadecenoic acid (8) and 11-octadecenoic acid (9) and two polyunsaturated fatty acids; 5,8,11,14-eicosatetraenoic acid (11) and 4,7,10,13,16,19-docosahexaenoic acid (12). Spectral analysis of a non-polar fraction eluted with hexane: diethyl ether (85: 15), resulted in the identification of eight steroids including: cholesta-5,22-dien-3β-ol (13), cholest-5-en-3β-ol (14), ergosta-5,22-dien-3β-ol (15), ergost-5-en-3β-ol (16), stigmasta-5,22-dien-3β-ol (17), γ-sitosterol (18), 33-norgorgosta-5,24(28)-dien-3β-ol (19) and stigmasta-5,24(28)-dien-3β-ol (20). Fatty acids-containing fraction was active against HT-29 cell line with IC50 26.52 ± 8.19 μg/mL, while the steroids-rich fraction was active against the three above mentioned cell lines with IC50 values of 1.20 ± 0.24, 4.12 ± 0.40 and 2.47 ± 0.31 μg/mL, respectively. All of the above-mentioned fractions and sub-fractions were inactive (IC50s > 50 μg/mL) when assayed against normal fibroblast cells. CONCLUSION: The present study suggests A. sinoxea as a potential natural source of cancer chemotherapeutics. Graphical abstract Cytotxic constituents of Axinella sinoxea.
Authors: Eoin Fahy; Shankar Subramaniam; H Alex Brown; Christopher K Glass; Alfred H Merrill; Robert C Murphy; Christian R H Raetz; David W Russell; Yousuke Seyama; Walter Shaw; Takao Shimizu; Friedrich Spener; Gerrit van Meer; Michael S VanNieuwenhze; Stephen H White; Joseph L Witztum; Edward A Dennis Journal: J Lipid Res Date: 2005-02-16 Impact factor: 5.922
Authors: Tatyana N Makarieva; Elena A Santalova; Irina A Gorshkova; Andrei S Dmitrenok; Alla G Guzii; Vladimir I Gorbach; Vassilii I Svetashev; Valentin A Stonik Journal: Lipids Date: 2002-01 Impact factor: 1.880