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Currently, surgery is often the best and most used approach, often preceded and followed by chemotherapy, which, however, carries serious short- and long-term side effects. Recently, much attention has been paid to natural compounds capable of inducing tumor cell death, reducing tumor and metastatic activity, and interacting with selective chemotherapy targeting tumor cells. Griffonia simplicifolia, a tropical African plant, has attracted attention because its extracts with bioactive chemicals have demonstrated multiple therapeutic uses. We show the antitumor properties of a Griffonia seed extract, obtained by maceration in a hydroalcoholic mixture (ethanol\/water, 70\/30, v\/v, Gri70), on osteosarcoma cell lines, evaluating cytotoxicity, interaction with a pro-inflammatory signal (interleukin-1\u03b2), epigenetic activity of this signal on interleukin-6 gene expression, and interactions with an elective chemotherapeutic agent, doxorubicin. Although the extract did not have strong antiproliferative activity in the cell lines analyzed, we nevertheless observed that it was able to block proliferative and migration signals induced by interleukin-1\u03b2, as well as acting epigenetically by blocking the de-methylation of the interleukin-6 promoter and its expression. Furthermore, the extract did not appear to interfere with the antitumor activity of doxorubicin, and the interaction potentiated antimetastatic effects. These results indicate that Gri-70 extract may be useful as adjuvants to enhance the effect of doxorubicin, reducing the adverse effects associated with the increased EMT process of osteosarcoma cells that manage to overcome cell death induction. Indeed, metastasis represents the main cause of poor prognosis.<\/jats:p>","DOI":"10.3390\/antiox15020263","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T13:47:02Z","timestamp":1771508822000},"page":"263","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antimetastatic Effects of a Griffonia simplicifolia Seed Extract in Osteosarcoma Cell Lines"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3308-9112","authenticated-orcid":false,"given":"Daniele","family":"Bellavia","sequence":"first","affiliation":[{"name":"IRCCS Istituto Ortopedico Rizzoli, SC Scienze e Tecnologie Chirurgiche, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8075-0642","authenticated-orcid":false,"given":"Flores","family":"Naselli","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5479-6145","authenticated-orcid":false,"given":"Graziella","family":"Serio","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128 Palermo, Italy"},{"name":"Fondazione Umberto Veronesi ETS, 20121 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4590-9052","authenticated-orcid":false,"given":"Paola Miriam","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2425-6460","authenticated-orcid":false,"given":"Viviana","family":"Costa","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Ortopedico Rizzoli, SC Scienze e Tecnologie Chirurgiche, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5493-9441","authenticated-orcid":false,"given":"Angela","family":"De Luca","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Ortopedico Rizzoli, SC Scienze e Tecnologie Chirurgiche, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9394-2002","authenticated-orcid":false,"given":"Lavinia","family":"Raimondi","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Ortopedico Rizzoli, SC Scienze e Tecnologie Chirurgiche, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5861-3342","authenticated-orcid":false,"given":"Carla","family":"Gentile","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7659-7312","authenticated-orcid":false,"given":"Fabio","family":"Caradonna","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128 Palermo, Italy"},{"name":"National Biodiversity Future Center (NBFC), 90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7843-5969","authenticated-orcid":false,"given":"Gianluca","family":"Giavaresi","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Ortopedico Rizzoli, SC Scienze e Tecnologie Chirurgiche, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"ref_1","unstructured":"Prater, S., and McKeon, B. 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