Sea cucumber sulfated polysaccharides extract potentiates the anticancer effect of 5- fluorouracil on hepatocellular carcinoma cells

Abstract Sea cucumber represents a potential marine source of high value compounds with medicinal properties especially its anti-cancer activity. Sea cucumbers contain numerous biomolecules, including sulfated polysaccharides (Ps) which have enormous therapeutic and nutraceutical potential. This stu...

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Main Authors: Samah E. Ismail, Neveen A. Hussein, Mona M. Rashad, Amany M. El-Sikaily, Abd El-Latif A. Hassanin, Esmail M. El-Fakharany
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-06496-7
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author Samah E. Ismail
Neveen A. Hussein
Mona M. Rashad
Amany M. El-Sikaily
Abd El-Latif A. Hassanin
Esmail M. El-Fakharany
author_facet Samah E. Ismail
Neveen A. Hussein
Mona M. Rashad
Amany M. El-Sikaily
Abd El-Latif A. Hassanin
Esmail M. El-Fakharany
author_sort Samah E. Ismail
collection DOAJ
description Abstract Sea cucumber represents a potential marine source of high value compounds with medicinal properties especially its anti-cancer activity. Sea cucumbers contain numerous biomolecules, including sulfated polysaccharides (Ps) which have enormous therapeutic and nutraceutical potential. This study aimed to investigate anticancer effect of Ps extracted from sea cucumbers on hepatocellular carcinoma. This study was in vitro study conducted on HepG-2 cells and normal wish cells that were divided into four groups: Group I including untreated cells, Group II including cells treated with different concentrations of 5-FU, Group III including cells treated with various concentrations of Ps extract. Group IV including cells treated with different concentrations of combined 5-FU and Ps extract. The extracted Ps were characterized using FT-IR, HPLC, and GC–MS. The anticancer effect of Ps extract was determined using cytotoxicity MTT assay, DNA fragmentation assay, wound healing assay, colony formation and soft agar assay. Also, the effect of Ps extract on VEGF, survivin, BAX and BID gene expression was determined by qRT-PCR and its effect on Bcl2 and BAK protein level was determined by western blotting technique. The results indicated that sea cucumber Ps extract either alone or in combination with 5-FU reduced HepG-2 and wish cell viability with higher selectivity index. Also, it inhibited both adherent and non-adherent colony forming ability and cell migration of HepG-2 cells. Moreover, it was significantly downregulated VEGF, survivin and Bcl2 while, it was significantly upregulated BAX, BAK and BID. In conclusion, sea cucumber Ps extract may be an effective chemotherapeutic agent against HCC.
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spelling doaj-art-18fe0de2c7d646f4b44994dea4bc9c832025-08-20T03:24:22ZengNature PortfolioScientific Reports2045-23222025-06-0115111510.1038/s41598-025-06496-7Sea cucumber sulfated polysaccharides extract potentiates the anticancer effect of 5- fluorouracil on hepatocellular carcinoma cellsSamah E. Ismail0Neveen A. Hussein1Mona M. Rashad2Amany M. El-Sikaily3Abd El-Latif A. Hassanin4Esmail M. El-Fakharany5Applied Medical Chemistry Department, Medical Research Institute, Alexandria UniversityApplied Medical Chemistry Department, Medical Research Institute, Alexandria UniversityApplied Medical Chemistry Department, Medical Research Institute, Alexandria UniversityMarine Pollution Department, National Institute of Oceanography and Fisheries, Ministry of Higher Education and Scientific ResearchMarine Biotechnology Department, National Institute of Oceanography and Fisheries, Ministry of Higher Education and Scientific ResearchProtein Research Department, Genetic Engineering and Biotechnology Research Institute, City for Scientific Research and Technology ApplicationsAbstract Sea cucumber represents a potential marine source of high value compounds with medicinal properties especially its anti-cancer activity. Sea cucumbers contain numerous biomolecules, including sulfated polysaccharides (Ps) which have enormous therapeutic and nutraceutical potential. This study aimed to investigate anticancer effect of Ps extracted from sea cucumbers on hepatocellular carcinoma. This study was in vitro study conducted on HepG-2 cells and normal wish cells that were divided into four groups: Group I including untreated cells, Group II including cells treated with different concentrations of 5-FU, Group III including cells treated with various concentrations of Ps extract. Group IV including cells treated with different concentrations of combined 5-FU and Ps extract. The extracted Ps were characterized using FT-IR, HPLC, and GC–MS. The anticancer effect of Ps extract was determined using cytotoxicity MTT assay, DNA fragmentation assay, wound healing assay, colony formation and soft agar assay. Also, the effect of Ps extract on VEGF, survivin, BAX and BID gene expression was determined by qRT-PCR and its effect on Bcl2 and BAK protein level was determined by western blotting technique. The results indicated that sea cucumber Ps extract either alone or in combination with 5-FU reduced HepG-2 and wish cell viability with higher selectivity index. Also, it inhibited both adherent and non-adherent colony forming ability and cell migration of HepG-2 cells. Moreover, it was significantly downregulated VEGF, survivin and Bcl2 while, it was significantly upregulated BAX, BAK and BID. In conclusion, sea cucumber Ps extract may be an effective chemotherapeutic agent against HCC.https://doi.org/10.1038/s41598-025-06496-7Sea cucumberSulphated polysaccharidesAngiogenesisApoptosisHepatocellular carcinoma
spellingShingle Samah E. Ismail
Neveen A. Hussein
Mona M. Rashad
Amany M. El-Sikaily
Abd El-Latif A. Hassanin
Esmail M. El-Fakharany
Sea cucumber sulfated polysaccharides extract potentiates the anticancer effect of 5- fluorouracil on hepatocellular carcinoma cells
Scientific Reports
Sea cucumber
Sulphated polysaccharides
Angiogenesis
Apoptosis
Hepatocellular carcinoma
title Sea cucumber sulfated polysaccharides extract potentiates the anticancer effect of 5- fluorouracil on hepatocellular carcinoma cells
title_full Sea cucumber sulfated polysaccharides extract potentiates the anticancer effect of 5- fluorouracil on hepatocellular carcinoma cells
title_fullStr Sea cucumber sulfated polysaccharides extract potentiates the anticancer effect of 5- fluorouracil on hepatocellular carcinoma cells
title_full_unstemmed Sea cucumber sulfated polysaccharides extract potentiates the anticancer effect of 5- fluorouracil on hepatocellular carcinoma cells
title_short Sea cucumber sulfated polysaccharides extract potentiates the anticancer effect of 5- fluorouracil on hepatocellular carcinoma cells
title_sort sea cucumber sulfated polysaccharides extract potentiates the anticancer effect of 5 fluorouracil on hepatocellular carcinoma cells
topic Sea cucumber
Sulphated polysaccharides
Angiogenesis
Apoptosis
Hepatocellular carcinoma
url https://doi.org/10.1038/s41598-025-06496-7
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