{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T05:32:48Z","timestamp":1767677568555,"version":"3.48.0"},"reference-count":55,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007771","name":"Medical University of Silesia","doi-asserted-by":"publisher","award":["BNW-1-022\/K\/5\/O"],"award-info":[{"award-number":["BNW-1-022\/K\/5\/O"]}],"id":[{"id":"10.13039\/100007771","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The glioblastoma multiforme (GBM) microenvironment, characterized by hypoxia and inflammation, is a principal driver of therapeutic resistance. Although natural compounds such as Caffeic Acid Phenethyl Ester (CAPE) are investigated for their anti-neoplastic properties, their bioactivity within the distinct metabolic landscape of the tumor core remains to be fully elucidated. Taking advantage of the recognized immunomodulatory properties of CAPE and its ability to cross the blood\u2013brain barrier, we hypothesized that hypoxia is a key factor determining its effect on glioma-associated inflammation. To test this hypothesis, we investigated the immunomodulatory effects of CAPE on the human astrocytoma cell line CCF-STTG1. Cells were cultured under normoxic and hypoxic conditions, stimulated with lipopolysaccharide (LPS) and interferon-alpha (IFN-\u03b1) to induce an inflammatory phenotype, and subsequently treated with CAPE. The secretion profiles of key cytokines (IL-8, IL-10, IL-26) and matrix metalloproteinases (MMPs) as well as pentraxin-3 (PTX-3) were then quantified using a multiplex immunoassay. Our results revealed a striking functional dichotomy. Under normoxic conditions, CAPE suppressed the secretion of key pro-inflammatory mediators. Conversely, under hypoxic conditions, CAPE significantly amplified the release of pro-tumorigenic factors, including the mediator facilitating tumor cell migration, invasion, and angiogenesis such as IL-8 and the invasion-associated metalloproteinase MMP-2. These findings suggesting that hypoxia may fundamentally reprograms the immunomodulatory potential of CAPE. However, due to limitations of study requires further validation in a broader panel of glioblastoma models.<\/jats:p>","DOI":"10.3390\/molecules31010140","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T18:10:51Z","timestamp":1767204651000},"page":"140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hypoxia-Driven Functional Conversion of CAPE: From Anti-Inflammatory to Pro-Tumorigenic Action in the Human Astrocytoma Cell Line CCF-SSTG1"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2006-6715","authenticated-orcid":false,"given":"Anna","family":"Kurek-G\u00f3recka","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9266-2292","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"K\u0142\u00f3sek","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gra\u017cyna","family":"Pietsz","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6173-2702","authenticated-orcid":false,"given":"Rados\u0142aw","family":"Balwierz","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, University of Opole, Oleska 48, 45-052 Opole, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8216-4495","authenticated-orcid":false,"given":"Zenon P.","family":"Czuba","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1007\/s12192-018-0915-0","article-title":"Caffeic Acid Phenethyl Ester (CAPE) Possesses pro-Hypoxia and Anti-Stress Activities: Bioinformatics and Experimental Evidences","volume":"23","author":"Bhargava","year":"2018","journal-title":"Cell Stress Chap-Erones"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.3892\/etm.2015.2346","article-title":"Therapeutic Potential of Caffeic Acid Phenethyl Ester and Its An-ti-Inflammatory and Immunomodulatory Effects (Review)","volume":"9","author":"Armutcu","year":"2015","journal-title":"Exp. 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