Cytotoxic metabolites from Callyspongia siphonella display antiproliferative activity by inducing apoptosis in HCT-116 cells
Tariq R.A. Sobahi1, Seif-Eldin N Ayyad2, Ahmed Abdel-Lateff3, Mardi M Algandaby4, Hajer S Alorfi1, Ashraf B Abdel-Naim5
1 Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
2 Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Chemistry, Faculty of Science, Damietta University, Damietta, Egypt
3 Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia, Egypt
4 Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
5 Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
Prof. Ahmed Abdel-Lateff
Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
Source of Support: None, Conflict of Interest: None
Objectives: To evaluate the antiproliferative effect of the isolated metabolites from Callyspongia siphonella. Methods: Different chromatographic methods have been done on the organic extract of the marine sponge aiming at isolating the bioactive metabolites. The cytotoxicity of the isolated compounds has been evaluated against the human colorectal cancer cell line; HCT-116, employing SRB assay. The flow cytometry assay was applied to measure the cell cycle analysis. Results: Six metabolites (1–6) were obtained. The compounds 4–6 exhibited IC50 values (µM ± SD) of 95.80± 1.34, 14.8 ± 2.33, and 19.8 ± 3.78, respectively. Cell cycle distribution analysis revealed that sipholenol A (5) and sipholenol L (6) induced G2/M and S phase arrest with concomitant increase in the pre-G cell population. Furthermore, 5 and 6 increased the nuclear expression of the pro-apoptotic protein-cleaved caspase-3 that effectively drives cellular apoptosis via caspase-3-dependent pathway. Conclusions: The antiproliferative activity of 5 and 6 can be recognized, at least partly, due to their ability to induce cellular apoptosis.
Abbreviations used: A549 (human lung carcinoma), Caco-2 (Human ColonCarcinoma), CHCl3 (Chloroform), HCT 116 (Human Colon Carcinoma), HepG2 (Liver Hepatocellular Carcinoma), HT-29 (Human Colorectal Adenocarcinoma), MCF-7 (Michigan Cancer Foundation-7; Human Breast Adenocarcinoma), MeOH (Methanol), NMR Nuclear Magnetic Resonance), PBS (Phosphate Buffered Saline), PC-3 (Human Prostate Cancer), PTLC (Preparative Thin Layer Chromatography), RPMI-1640 (Roswell Park Memorial Institute medium), TLC (ThinLayer Chromatography).