Evaluation of cytotoxic, apoptotic effects and phenolic compounds of sea cucumber Holothuria tubulosa (Gmelin, 1791) extracts


Abstract: This study aimed to investigate the potential cytotoxic effects and phenolic contents of aqueous (HTS) and methanolic (HTM) extracts of Holothuria tubulosa gathered from Muğla (Turkey) against different cancer cells for the first time. An MTT assay was carried out to determine cellular viability. Apoptotic cell death was determined using flow cytometry. DNA fragmentation assay and caspase-3 activity analysis were carried out. Both extracts were analyzed by high performance liquid chromatography (HPLC) for quantification of phenolic compounds. Both HTS and HTM extracts generally caused a decrease in the cell viability in a concentration- and timedependent manner. The lowest IC$_{50}$ value was found in the HeLa cell line with 21.01 μg/mL for the HTS extract at 72 h. Both extracts are capable of significantly enhancing the apoptotic process in HeLa and A549 cells, causing DNA fragmentation, and also increasing activity of caspase-3 in both these cell lines, especially after treatment with at 500 μg/mL. Based on HPLC analysis, the most abundant component was epicatechin (790.091 μg/g extract) and 2.5 dihydroxybenzoic acid (153.890 μg/g extract) in the HTS and HTM extracts, respectively. This is the first study showing potential cytotoxic activity of H. tubulosa extracts from Muğla, Turkey against human cancer cells. Our results suggest that H. tubulosa may be a good source for development of anticancer agents.

Keywords: Holothuria tubulosa, cancer cell lines, cytotoxicity, apoptosis, HPLC analysis

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