{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T18:05:10Z","timestamp":1792865110241,"version":"4.5.0"},"reference-count":48,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T00:00:00Z","timestamp":1598227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["308595\/2016-5"],"award-info":[{"award-number":["308595\/2016-5"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006181","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado da Bahia","doi-asserted-by":"publisher","award":["APP006\/2016"],"award-info":[{"award-number":["APP006\/2016"]}],"id":[{"id":"10.13039\/501100006181","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Due to its importance in the pathogenesis of oral squamous cell carcinoma (OSCC), the Hedgehog (HH) pathway is considered a potential therapeutic target. We investigated the effects of GANT61, a GLI inhibitor, on HH gene expression, as well as on metastatic OSCC cell proliferation and death. Following culture in DMEM medium, cytotoxicity of GANT61 against different tumor and non-tumor cell types was assessed by alamarBlue assays. Cytotoxicity analysis revealed that the metastatic HSC3 cell line was the most sensitive (IC50: 36 \u00b5M) to the tested compound. The compound\u2019s effects on the expression of HH pathways components were analyzed by qPCR and Western blot; cell viability was analyzed by trypan blue assay and flow cytometry were used to investigate cell cycle phase, morphology, and death patterns in HSC3 cells. A significant reduction in mRNA levels of the GLI1 transcription factor was found after 12 h of treatment withGANT61. Protein expression levels of other HH pathway components (PTCH1, SHH, and Gli1) and HSC3 cell viability also decreased after 24 h of treatment. Cell cycle analysis and death pattern evaluations revealed significantly increased nuclear fragmentation in sub-G1 phase, as well as cell death due to apoptosis. In conclusion, the significantly reduced GLI1 gene expression seen in response to the GLI inhibitor indicates diminished downstream activation in HH pathway components. GANT61 significantly reduced cell viability in the metastatic cell line of OSCC and promoted a significant increase in nuclear fragmentation and cell death by apoptosis.<\/jats:p>","DOI":"10.3390\/ijms21176076","type":"journal-article","created":{"date-parts":[[2020,8,23]],"date-time":"2020-08-23T21:28:06Z","timestamp":1598218086000},"page":"6076","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["GANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cells"],"prefix":"10.3390","volume":"21","author":[{"given":"Ta\u00eds","family":"Bacelar Sacramento de Ara\u00fajo","sequence":"first","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ\/BA), Salvador 40296-710, Bahia, Brazil"},{"name":"Department of Propedeutics, Faculty of Dentistry, Federal University of Bahia, Salvador 40110-909, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"de Oliveira Siquara da Rocha","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ\/BA), Salvador 40296-710, Bahia, Brazil"},{"name":"Department of Propedeutics, Faculty of Dentistry, Federal University of Bahia, Salvador 40110-909, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Torres Andion Vidal","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ\/BA), Salvador 40296-710, Bahia, Brazil"},{"name":"Department of Propedeutics, Faculty of Dentistry, Federal University of Bahia, Salvador 40110-909, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Lucas","family":"Cerqueira Coelho","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ\/BA), Salvador 40296-710, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3051-9060","authenticated-orcid":false,"given":"Mitermayer","family":"Galv\u00e3o dos Reis","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ\/BA), Salvador 40296-710, Bahia, Brazil"},{"name":"Department of Pathology, School of Medicine, Federal University of Bahia (UFBA), Salvador 40110-909, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Solano de Freitas Souza","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ\/BA), Salvador 40296-710, Bahia, Brazil"},{"name":"D\u2019Or Institute for Research and Education (IDOR), Sao Rafael Hospital, Salvador 41253-190, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7549-2992","authenticated-orcid":false,"given":"Milena","family":"Botelho Pereira Soares","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ\/BA), Salvador 40296-710, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago","family":"Almeida Pereira","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Della Coletta","sequence":"additional","affiliation":[{"name":"Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba 13414-903, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6774-2063","authenticated-orcid":false,"given":"Daniel","family":"Pereira Bezerra","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ\/BA), Salvador 40296-710, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosane","family":"Borges Dias","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ\/BA), Salvador 40296-710, Bahia, Brazil"},{"name":"Department of Propedeutics, Faculty of Dentistry, Federal University of Bahia, Salvador 40110-909, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8922-2985","authenticated-orcid":false,"given":"Clarissa","family":"Ara\u00fajo Gurgel Rocha","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ\/BA), Salvador 40296-710, Bahia, Brazil"},{"name":"Department of Propedeutics, Faculty of Dentistry, Federal University of Bahia, Salvador 40110-909, Bahia, Brazil"},{"name":"Department of Pathology, School of Medicine, Federal University of Bahia (UFBA), Salvador 40110-909, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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