Anticancer Activity of Holothuria Leucospilota-Derived Saponin on MKN45 Gastric Cancer Cell via Upregulation of CDH1 Hub Gene
Background: The treatment of gastric cancer (GC) is still quite challenging. Yet, marine invertebrates have been found to produce a wide range of anticancer bioactive compounds that show promise in fighting cancer. The present study aimed to evaluate whether saponin derived from Holothuria leucospil...
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| Format: | Article |
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Shiraz University of Medical Sciences
2025-01-01
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| Series: | Middle East Journal of Cancer |
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| Online Access: | https://mejc.sums.ac.ir/article_50008_589414eac0efe8894747bf1c3715750d.pdf |
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| author | Khadijeh Sadegh Amirhossein Ahmadi Ahmad Shadi Ahmad Ghasemi |
| author_facet | Khadijeh Sadegh Amirhossein Ahmadi Ahmad Shadi Ahmad Ghasemi |
| author_sort | Khadijeh Sadegh |
| collection | DOAJ |
| description | Background: The treatment of gastric cancer (GC) is still quite challenging. Yet, marine invertebrates have been found to produce a wide range of anticancer bioactive compounds that show promise in fighting cancer. The present study aimed to evaluate whether saponin derived from Holothuria leucospilata (H. Leucospilota), a species of sea cucumber, possesses anticancer activity against GC cells.Method: In this experimental study, the cytotoxic effect of H. Leucospilota-derived n-butanol fraction saponins (HLBS) sourced from the Persian Gulf on MKN45 GC cells was evaluated through tetrazolium salt and colony formation assays. The effect of HLBS on MKN45 cell migration, cell cycle, and apoptosis was assessed using a scratch assay, and flow cytometry, respectively. Hub genes of GC were identified through bioinformatics analysis. The effects of HLBS on the expression of the two top-ranked GC hub genes were measured using real-time polymerase chain reaction. Comparisons between groups were performed using the ANOVA test by GraphPad Prism software at the statistically significant P-value <0.05.Results: HLBS with an IC50 concentration of 75 μg/ml at 48 hours resulted in a significant decrease in cell viability, clonogenic ability (46.63% reduction, P < 0.01), and migration of MKN45 cells (74.5% reduction, P < 0.01). Moreover, HLBS led to an increase of approximately 21 and 13% in the S-phase and apoptotic cell populations, respectively. HLBS also upregulated the expression of CDH1, as a highly ranked hub gene associated with GC (P < 0.05).Conclusion: The inhibitory effect of HLBS on MKN45 cells suggests HLBS as a candidate for further drug discovery programs in GC research, and paves the way to introduce new anticancer HLBS synthetic derivatives. |
| format | Article |
| id | doaj-art-38e1db0b9de144f3b82eba8875d3bbaa |
| institution | Kabale University |
| issn | 2008-6709 2008-6687 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Shiraz University of Medical Sciences |
| record_format | Article |
| series | Middle East Journal of Cancer |
| spelling | doaj-art-38e1db0b9de144f3b82eba8875d3bbaa2025-01-13T05:34:02ZengShiraz University of Medical SciencesMiddle East Journal of Cancer2008-67092008-66872025-01-01161243810.30476/mejc.2024.100200.197650008Anticancer Activity of Holothuria Leucospilota-Derived Saponin on MKN45 Gastric Cancer Cell via Upregulation of CDH1 Hub GeneKhadijeh Sadegh0Amirhossein Ahmadi1Ahmad Shadi2Ahmad Ghasemi3Department of Biological Science and Technology, Faculty of Nano- and Bio-Science and Technology, Persian Gulf University, Bushehr, IranDepartment of Biological Science and Technology, Faculty of Nano- and Bio-Science and Technology, Persian Gulf University, Bushehr, IranDepartment of Biological Science and Technology, Faculty of Nano- and Bio-Science and Technology, Persian Gulf University, Bushehr, IranPersian Gulf Research Institute, Persian Gulf University, Bushehr, IranBackground: The treatment of gastric cancer (GC) is still quite challenging. Yet, marine invertebrates have been found to produce a wide range of anticancer bioactive compounds that show promise in fighting cancer. The present study aimed to evaluate whether saponin derived from Holothuria leucospilata (H. Leucospilota), a species of sea cucumber, possesses anticancer activity against GC cells.Method: In this experimental study, the cytotoxic effect of H. Leucospilota-derived n-butanol fraction saponins (HLBS) sourced from the Persian Gulf on MKN45 GC cells was evaluated through tetrazolium salt and colony formation assays. The effect of HLBS on MKN45 cell migration, cell cycle, and apoptosis was assessed using a scratch assay, and flow cytometry, respectively. Hub genes of GC were identified through bioinformatics analysis. The effects of HLBS on the expression of the two top-ranked GC hub genes were measured using real-time polymerase chain reaction. Comparisons between groups were performed using the ANOVA test by GraphPad Prism software at the statistically significant P-value <0.05.Results: HLBS with an IC50 concentration of 75 μg/ml at 48 hours resulted in a significant decrease in cell viability, clonogenic ability (46.63% reduction, P < 0.01), and migration of MKN45 cells (74.5% reduction, P < 0.01). Moreover, HLBS led to an increase of approximately 21 and 13% in the S-phase and apoptotic cell populations, respectively. HLBS also upregulated the expression of CDH1, as a highly ranked hub gene associated with GC (P < 0.05).Conclusion: The inhibitory effect of HLBS on MKN45 cells suggests HLBS as a candidate for further drug discovery programs in GC research, and paves the way to introduce new anticancer HLBS synthetic derivatives.https://mejc.sums.ac.ir/article_50008_589414eac0efe8894747bf1c3715750d.pdfstomach neoplasmssea cucumbercadherinscomputational biology |
| spellingShingle | Khadijeh Sadegh Amirhossein Ahmadi Ahmad Shadi Ahmad Ghasemi Anticancer Activity of Holothuria Leucospilota-Derived Saponin on MKN45 Gastric Cancer Cell via Upregulation of CDH1 Hub Gene Middle East Journal of Cancer stomach neoplasms sea cucumber cadherins computational biology |
| title | Anticancer Activity of Holothuria Leucospilota-Derived Saponin on MKN45 Gastric Cancer Cell via Upregulation of CDH1 Hub Gene |
| title_full | Anticancer Activity of Holothuria Leucospilota-Derived Saponin on MKN45 Gastric Cancer Cell via Upregulation of CDH1 Hub Gene |
| title_fullStr | Anticancer Activity of Holothuria Leucospilota-Derived Saponin on MKN45 Gastric Cancer Cell via Upregulation of CDH1 Hub Gene |
| title_full_unstemmed | Anticancer Activity of Holothuria Leucospilota-Derived Saponin on MKN45 Gastric Cancer Cell via Upregulation of CDH1 Hub Gene |
| title_short | Anticancer Activity of Holothuria Leucospilota-Derived Saponin on MKN45 Gastric Cancer Cell via Upregulation of CDH1 Hub Gene |
| title_sort | anticancer activity of holothuria leucospilota derived saponin on mkn45 gastric cancer cell via upregulation of cdh1 hub gene |
| topic | stomach neoplasms sea cucumber cadherins computational biology |
| url | https://mejc.sums.ac.ir/article_50008_589414eac0efe8894747bf1c3715750d.pdf |
| work_keys_str_mv | AT khadijehsadegh anticanceractivityofholothurialeucospilotaderivedsaponinonmkn45gastriccancercellviaupregulationofcdh1hubgene AT amirhosseinahmadi anticanceractivityofholothurialeucospilotaderivedsaponinonmkn45gastriccancercellviaupregulationofcdh1hubgene AT ahmadshadi anticanceractivityofholothurialeucospilotaderivedsaponinonmkn45gastriccancercellviaupregulationofcdh1hubgene AT ahmadghasemi anticanceractivityofholothurialeucospilotaderivedsaponinonmkn45gastriccancercellviaupregulationofcdh1hubgene |