{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:07:11Z","timestamp":1762866431696,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai, UAE","award":["MBRU-CM-RG2020-07"],"award-info":[{"award-number":["MBRU-CM-RG2020-07"]}]},{"name":"Al Jalila Foundation-funded MBRU Postdoctoral Fellowship Awards"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. The search for effective, new antineoplastic drugs with fewer side effects for the treatment of CRC continues, with marine-derived compounds emerging as promising candidates. Objectives: This study investigates the anticancer potential of Frondanol, a nutraceutical derived from the Atlantic Sea cucumber Cucumaria frondosa, known for its potent anti-inflammatory properties. Methods: Two human CRC cell lines, Caco-2 and HT-29, were used to test the effects of Frondanol using various in vitro approaches. Results: Frondanol significantly inhibited cell viability in a dose- and time-dependent manner. At a 1:10,000 dilution, viability decreased to around 30% in Caco-2 and 20% in HT-29 after 24 h, dropping to nearly 5% at 48 h. Furthermore, a clonogenic assay showed around 50% reduction in colony formation in both cell lines. Flow cytometry-based Annexin V staining revealed that Frondanol increased early apoptosis to ~5.2% in Caco-2 and ~9.4% in HT-29 cells, while cell cycle analysis showed accumulation of the sub G0 (apoptotic) phase increasing from 1.5% to 14.7% (Caco-2) and from 1.9% to 23.8% (HT-29). At the molecular level, Frondanol treatment significantly decreased anti-apoptotic protein B-cell lymphoma (Bcl)-2 expression while increasing the expression of the proapoptotic protein Bcl-2-associated X-protein. Additionally, Frondanol markedly induced cytochrome c release from the mitochondria and activated caspase-9, caspase-7, and caspase-3 after treatment, alongside cleavage of the caspase-3 substrate poly (ADP-ribose) polymerase. Frondanol inhibited 5-lipoxygenase activity, further contributing to its anticancer effects. Conclusions: In conclusion, Frondanol inhibits CRC cell proliferation and induces apoptosis through the mitochondrial pathway in vitro, suggesting that it is a potential nutraceutical for the prevention of human colorectal cancer or a valuable source of anticancer compounds.<\/jats:p>","DOI":"10.3390\/ph18111714","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T12:44:55Z","timestamp":1762865095000},"page":"1714","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effects of Frondanol, a Non-Polar Extract of the Atlantic Sea Cucumber, in Colon Cancer Cells"],"prefix":"10.3390","volume":"18","author":[{"given":"Hardik","family":"Ghelani","sequence":"first","affiliation":[{"name":"College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health, Dubai P.O. Box 505055, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6318-3697","authenticated-orcid":false,"given":"Hala","family":"Altaher","sequence":"additional","affiliation":[{"name":"College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health, Dubai P.O. Box 505055, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hadil","family":"Sarsour","sequence":"additional","affiliation":[{"name":"College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health, Dubai P.O. Box 505055, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marah","family":"Tabbal","sequence":"additional","affiliation":[{"name":"College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health, Dubai P.O. Box 505055, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally","family":"Badawi","sequence":"additional","affiliation":[{"name":"College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health, Dubai P.O. Box 505055, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas E.","family":"Adrian","sequence":"additional","affiliation":[{"name":"College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health, Dubai P.O. Box 505055, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1685-5594","authenticated-orcid":false,"given":"Reem K.","family":"Jan","sequence":"additional","affiliation":[{"name":"College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health, Dubai P.O. Box 505055, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.3892\/mco.2021.2433","article-title":"General insight into cancer: An overview of colorectal cancer (Review)","volume":"15","author":"Alzahrani","year":"2021","journal-title":"Mol. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1136\/gutjnl-2022-327736","article-title":"Global burden of colorectal cancer in 2020 and 2040: Incidence and mortality estimates from GLOBOCAN","volume":"72","author":"Morgan","year":"2023","journal-title":"Gut"},{"key":"ref_3","first-page":"366","article-title":"Worldwide variations in colorectal cancer","volume":"59","author":"Center","year":"2009","journal-title":"CA Cancer J. 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