The Ω-3 fatty acid docosahexaenoic acid selectively induces apoptosis in tumor-derived cells and suppress tumor growth in gastric cancer

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dc.contributor.authorOrtega, Lorena
dc.contributor.authorLobos-González, Lorena
dc.contributor.authorReyna-Jeldes, Mauricio
dc.contributor.authorCerda, Daniela
dc.contributor.authorDe la Fuente-Ortega, Erwin
dc.contributor.authorCastro, Patricio
dc.contributor.authorBernal, Giuliano
dc.contributor.authorCoddou, Claudio
dc.date.accessioned2022-05-03T16:15:59Z
dc.date.available2022-05-03T16:15:59Z
dc.date.issued2021
dc.description.abstractDespite current achievements and innovations in cancer treatment, conventional chemotherapy has several limitations, such as unsatisfactory long-term survival, cancer drug resistance and toxicity against non-tumoral cells. In the search for safer therapeutic alternatives, docosahexaenoic acid (DHA) has shown promising effects inhibiting tumor growth without significant side effects in several types of cancer, but in gastric cancer (GC) its effects have not been completely described. In this study, we characterized the effects of DHA in GC using in vivo and in vitro models. Among all of the evaluated Ω-3 and Ω-6 fatty acids, DHA showed the highest antiproliferative potency and selectivity against the GC-derived cell line AGS. 10-100 μM DHA decreased AGS cell viability in a concentration-dependent manner but had no effect on non-tumoral GES-1 cells. To evaluate if the effects of DHA were due to apoptosis induction, cells were stained with Annexin V-PI, observing that 75 and 100 μM DHA increased apoptosis in AGS, but not in GES-1 cells. Additionally, levels of several proapoptotic and antiapoptotic regulators were assessed by qPCR, western blot and activity assays, showing similar results. In order to evaluate DHA efficacy in vivo, xenografts in an immunodeficient mouse model (BALB/cNOD-SCID) were used. In these experiments, DHA treatment for six weeks consistently reduced subcutaneous tumor size, ascitic fluid volume and liver metastasis. In summary, we found that DHA has a selective antiproliferative effect on GC, being this effect driven by apoptosis induction. Our investigation provides promising features for DHA as potential therapeutic agent in GC.es
dc.description.versionVersión Publicadaes
dc.identifier.citationOrtega L, Lobos-González L, Reyna-Jeldes M, Cerda D, De la Fuente-Ortega E, Castro P, Bernal G, Coddou C. The Ω-3 fatty acid docosahexaenoic acid selectively induces apoptosis in tumor-derived cells and suppress tumor growth in gastric cancer. Eur J Pharmacol. 2021 Apr 5;896:173910. doi: 10.1016/j.ejphar.2021.173910. Epub 2021 Jan 26. Erratum in: Eur J Pharmacol. 2021 Sep 5;906:174287. PMID: 33508285.es
dc.identifier.urihttps://doi.org/10.1016/j.ejphar.2021.173910es
dc.identifier.urihttp://hdl.handle.net/11447/6051
dc.language.isoenes
dc.subjectApoptosises
dc.subjectDHAes
dc.subjectDocosahexaenoic acides
dc.subjectGastric canceres
dc.subjectΩ-3 polyunsaturated fatty acidses
dc.titleThe Ω-3 fatty acid docosahexaenoic acid selectively induces apoptosis in tumor-derived cells and suppress tumor growth in gastric canceres
dc.typeArticlees
dcterms.sourceEuropean Journal of Pharmacologyes

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