Identification of Novel Cytotoxic Peptide KENPVLSLVNGMF from Marine Sponge Xestospongia testudinaria, with Characterization of Stability in Human Serum

Quah, Yixian and Mohd Ismail, Nor Ismaliza and Ooi, Jillian Lean Sim and Affendi, Yang Amri and Abd Manan, Fazilah and Wong, Fai Chu and Chai, Tsun Thai (2018) Identification of Novel Cytotoxic Peptide KENPVLSLVNGMF from Marine Sponge Xestospongia testudinaria, with Characterization of Stability in Human Serum. International Journal of Peptide Research and Therapeutics, 24 (1). pp. 189-199. ISSN 1573-3149

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Official URL: https://doi.org/10.1007/s10989-017-9604-6

Abstract

Resistance and side effects are common problems for anticancer drugs used in chemotherapy. Thus, continued research to discover novel and specific anticancer drugs is obligatory. Marine sponges hold great promise as a source of potent cytotoxic peptides with future applications in cancer treatments. This study aimed to purify and identify cytotoxic peptides from the protein hydrolysates of the giant barrel sponge Xestospongia testudinaria, guided by a cytotoxicity assay based on the human cervical cancer cell line (HeLa). Comparison among trypsin, chymotrypsin, papain and alcalase hydrolysates of X. testudinaria revealed papain hydrolysate (PH) to be the most active. PH was purified consecutively by membrane ultrafiltration, gel filtration chromatography, and reversed-phase high performance liquid chromatography (RP-HPLC). Following liquid chromatography-tandem mass spectrometric analysis, two peptides were identified from the most cytotoxic RP-HPLC fraction: KENPVLSLVNGMF and LLATIPKVGVFSILV. Between the two, only the synthetic peptide KENPVLSLVNGMF showed cytotoxicity toward HeLa cells in a dose-dependent manner. KENPVLSLVNGMF (EC50 0.67 mM) was 3.8-fold more cytotoxic compared with anticancer drug 5-fluorouracil (EC50 2.56 mM). Furthermore, KENPVLSLVNGMF show only marginal 5% cytotoxicity to Hek293, a non-cancerous, human embryonic kidney cell line, when tested at 0.67 mM. The half-life of the peptide was 3.2 ± 0.5 h in human serum in vitro, as revealed by RP-HPLC analyses. These results suggest that KENPVLSLVNGMF identified from X. testudinaria papain hydrolysate has potential applications as peptide lead in future development of potent and specific anticancer drugs.

Item Type: Article
Uncontrolled Keywords: Cancer; Cytotoxic peptide; Marine sponge; Peptide stability; Protein hydrolysate; Xestospongia testudinaria
Subjects: G Geography. Anthropology. Recreation
Q Science > Q Science (General)
Q Science > QH Natural history
Divisions: Faculty of Arts and Social Sciences
Faculty of Science > Institute of Biological Sciences
Deputy Vice Chancellor (Research & Innovation) Office > Institute of Ocean and Earth Sciences
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 18 Apr 2019 06:31
Last Modified: 18 Apr 2019 06:31
URI: http://eprints.um.edu.my/id/eprint/21003

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