{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T15:02:09Z","timestamp":1785164529232,"version":"3.55.0"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Colorectal cancer (CRC) treatment with standard chemotherapeutics such as capecitabine (CAP) and irinotecan (IRT) is frequently limited by toxicity and resistance. To identify novel adjuvant strategies, we investigated the dichloromethane\u2013methanol (DM) Soxhlet extract of the red alga Jania rubens, previously shown to exert intrinsic antiproliferative effects via reactive oxygen species (ROS) induction, inhibition of epithelial\u2013mesenchymal transition (EMT), and suppression of TET enzymes. The present study evaluated the effect of the DM extract in combination with chemotherapeutic agents in HCT-116, Caco-2, and HT-29 colorectal cancer cell lines, assessing its potential to enhance treatment response. Co-treatment with the DM extract significantly enhanced the cytotoxic and anti-migratory effects of CAP and IRT in HCT-116 and Caco-2 cells. Combination treatment also impaired long-term clonogenic survival, suggesting the inhibition of therapy-resistant subpopulations. Flow cytometric analysis (Annexin V-FITC\/PI) revealed a dose-dependent increase in apoptosis in HCT-116 cells following DM treatment. Western blot analysis further supported the pro-apoptotic activity of the DM extract by demonstrating reduced BCL-2 protein expression. The extract additionally modulated the mRNA expression levels of cytokines (TNF-\u03b1, IL-6, and IL-10), suggesting potential immunomodulatory effects in colorectal cancer cells. Notably, co-administration of IRT and the DM extract enhanced apoptosis, primarily through the downregulation of the anti-apoptotic gene BCL-2. Together, these findings indicate that the Jania rubens DM extract modulates multiple cellular pathways and enhances the response to conventional CRC chemotherapeutic agents.<\/jats:p>","DOI":"10.3390\/cimb48080759","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T14:08:14Z","timestamp":1785161294000},"page":"759","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Red Alga Jania rubens DM Extract Modulates Apoptotic and Inflammatory Pathways to Enhance Chemotherapeutic Response in Colorectal Cancer Cells"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6140-3108","authenticated-orcid":false,"given":"Zeina","family":"Radwan","sequence":"first","affiliation":[{"name":"Department of Anatomy, Cell Biology, and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 1107-2020, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maysam","family":"Moussa","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Health Sciences, University of Balamand, Al-Koura, Tripoli P.O. Box 100, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaza","family":"Khatib Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Health Sciences, University of Balamand, Al-Koura, Tripoli P.O. Box 100, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaymaa","family":"Al Sharif","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Health Sciences, University of Balamand, Al-Koura, Tripoli P.O. Box 100, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayan","family":"Kassir","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Biotechnology, AZM Center for Research in Biotechnology and Its Applications, Doctoral School for Sciences and Technology, Lebanese University, Tripoli 1300, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5573-7160","authenticated-orcid":false,"given":"Fatima","family":"El-Mched","sequence":"additional","affiliation":[{"name":"Department of Biological Science, Faculty of Science, Beirut Arab University, Tripoli P.O. Box 11-5020, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Haddad","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Health Sciences, University of Balamand, Al-Koura, Tripoli P.O. Box 100, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1862-5426","authenticated-orcid":false,"given":"Nadine","family":"Darwiche","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut P.O. Box 110236, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwan","family":"El-Sabban","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology, and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 1107-2020, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiba","family":"Mawlawi","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Biotechnology, AZM Center for Research in Biotechnology and Its Applications, Doctoral School for Sciences and Technology, Lebanese University, Tripoli 1300, Lebanon"},{"name":"Faculty of Public Health III, Lebanese University, Tripoli 1300, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeina","family":"Dassouki","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Health Sciences, University of Balamand, Al-Koura, Tripoli P.O. Box 100, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101174","DOI":"10.1016\/j.tranon.2021.101174","article-title":"Global colorectal cancer burden in 2020 and projections to 2040","volume":"14","author":"Xi","year":"2021","journal-title":"Transl. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"659","DOI":"10.7150\/ijms.24453","article-title":"New Trends in the Therapeutic Approach to Metastatic Colorectal Cancer","volume":"15","year":"2018","journal-title":"Int. J. Med. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Hossain, M.S., Karuniawati, H., Jairoun, A.A., Urbi, Z., Ooi, J., John, A., Lim, Y.C., Kibria, K.M.K., Mohiuddin, A.K.M., and Ming, L.C. (2022). 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