Identification of Novel Cytotoxic Peptide KENPVLSLVNGMF from Marine Sponge Xestospongia testudinaria, with Characterization of Stability in Human Serum
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....
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| Format: | Article |
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Springer Verlag
2018
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| author | Quah, Yixian Mohd Ismail, Nor Ismaliza Ooi, Jillian Lean Sim Affendi, Yang Amri Abd Manan, Fazilah Wong, Fai Chu Chai, Tsun Thai |
| author_facet | Quah, Yixian Mohd Ismail, Nor Ismaliza Ooi, Jillian Lean Sim Affendi, Yang Amri Abd Manan, Fazilah Wong, Fai Chu Chai, Tsun Thai |
| author_sort | Quah, Yixian |
| collection | UM |
| description | 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. |
| first_indexed | 2024-03-06T05:52:53Z |
| format | Article |
| id | um.eprints-21003 |
| institution | Universiti Malaya |
| last_indexed | 2024-03-06T05:52:53Z |
| publishDate | 2018 |
| publisher | Springer Verlag |
| record_format | dspace |
| spelling | um.eprints-210032019-04-18T06:31:25Z http://eprints.um.edu.my/21003/ Identification of Novel Cytotoxic Peptide KENPVLSLVNGMF from Marine Sponge Xestospongia testudinaria, with Characterization of Stability in Human Serum Quah, Yixian Mohd Ismail, Nor Ismaliza Ooi, Jillian Lean Sim Affendi, Yang Amri Abd Manan, Fazilah Wong, Fai Chu Chai, Tsun Thai G Geography. Anthropology. Recreation Q Science (General) QH Natural history 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. Springer Verlag 2018 Article PeerReviewed 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, DOI https://doi.org/10.1007/s10989-017-9604-6 <https://doi.org/10.1007/s10989-017-9604-6>. https://doi.org/10.1007/s10989-017-9604-6 doi:10.1007/s10989-017-9604-6 |
| spellingShingle | G Geography. Anthropology. Recreation Q Science (General) QH Natural history Quah, Yixian Mohd Ismail, Nor Ismaliza Ooi, Jillian Lean Sim Affendi, Yang Amri Abd Manan, Fazilah Wong, Fai Chu Chai, Tsun Thai Identification of Novel Cytotoxic Peptide KENPVLSLVNGMF from Marine Sponge Xestospongia testudinaria, with Characterization of Stability in Human Serum |
| title | Identification of Novel Cytotoxic Peptide KENPVLSLVNGMF from Marine Sponge Xestospongia testudinaria, with Characterization of Stability in Human Serum |
| title_full | Identification of Novel Cytotoxic Peptide KENPVLSLVNGMF from Marine Sponge Xestospongia testudinaria, with Characterization of Stability in Human Serum |
| title_fullStr | Identification of Novel Cytotoxic Peptide KENPVLSLVNGMF from Marine Sponge Xestospongia testudinaria, with Characterization of Stability in Human Serum |
| title_full_unstemmed | Identification of Novel Cytotoxic Peptide KENPVLSLVNGMF from Marine Sponge Xestospongia testudinaria, with Characterization of Stability in Human Serum |
| title_short | Identification of Novel Cytotoxic Peptide KENPVLSLVNGMF from Marine Sponge Xestospongia testudinaria, with Characterization of Stability in Human Serum |
| title_sort | identification of novel cytotoxic peptide kenpvlslvngmf from marine sponge xestospongia testudinaria with characterization of stability in human serum |
| topic | G Geography. Anthropology. Recreation Q Science (General) QH Natural history |
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