{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T17:30:48Z","timestamp":1776274248475,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T00:00:00Z","timestamp":1721692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Afyonkarahisar Health Sciences University Research Foundation","award":["21.GENEL.009"],"award-info":[{"award-number":["21.GENEL.009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: PIN1 is overexpressed in several human cancers, including prostate cancer, breast cancer, and oral squamous carcinomas. Juglone (J), derived from walnut, was reported to selectively inhibit PIN1 by modifying its sulfhydryl groups. In this study, the potential effects of juglone, also known as PIN1 inhibitor, on oral cancer and carcinogenesis were investigated at the molecular level. Materials and Methods: 4-Nitroquinoline N-oxide (4-NQO) was used to create an oral cancer model in animals. Wistar rats were divided into five groups: Control, NQO, Juglone, NQO+J, and NQO+J*. The control group received the basal diet and tap water throughout the experiment. The NQO group received 4-NQO for 8 weeks in drinking water only. The Juglone group was administered intraperitoneally in a juglone solution for 10 weeks (1 mg\/kg\/day). The NQO+J group received 4-NQO in drinking water for 8 weeks, starting 1 week after the cessation of 4-NQO treatment. They were then administered intraperitoneally in a juglone solution for 10 weeks. (1 mg\/kg\/day). NQO+J* group: received 4 NQO for 8 weeks in drinking water and administered intraperitoneally in a juglone solution for 10 weeks (1 mg\/kg\/day). They were sacrificed at the end of the 22-week experimental period. The tongue tissues of the rats were isolated after the experiment, morphological changes were investigated by histological examinations, and the molecular apoptotic process was investigated by rt-qPCR and western blot. Results: Histological results indicate that tumors are formed in the tongue tissue with 4-NQO, and juglone treatment largely corrects the epithelial changes that developed with 4-NQO. It has been determined that apoptotic factors p53, Bax, and caspases are induced by the effect of juglone, while antiapoptotic factors such as Bcl-2 are suppressed. However, it was observed that the positive effects were more pronounced in rats given juglone together with 4-NQO. Conclusions: The use of PIN1 inhibitors such as juglone in place of existing therapeutic approaches might be a promising and novel approach to the preservation and treatment of oral cancer and carcinogenesis. However, further research is required to investigate the practical application of such inhibitors.<\/jats:p>","DOI":"10.3390\/medicina60081192","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T11:40:36Z","timestamp":1721734836000},"page":"1192","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Impact of Juglone, a PIN1 \u0130nhibitor, on Oral Carcinogenesis Induced by 4-Nitroquinoline-1-Oxide (4NQO) in Rat Model"],"prefix":"10.3390","volume":"60","author":[{"given":"Olgun","family":"Topal","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Afyonkarahisar Health Sciences University, 03200 Afyonkarahisar, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9932-9169","authenticated-orcid":false,"given":"Burcu G\u00fc\u00e7yetmez","family":"Topal","sequence":"additional","affiliation":[{"name":"Department of Pedodontics, Faculty of Dentistry, Afyonkarahisar Health Sciences University, 03200 Afyonkarahisar, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunus","family":"Ba\u015f","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Afyonkarahisar Health Sciences University, 03200 Afyonkarahisar, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00fcnyamin","family":"Ongan","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Afyonkarahisar Health Sciences University, 03200 Afyonkarahisar, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00f6khan","family":"Sadi","sequence":"additional","affiliation":[{"name":"Department of Biology, K.O. Science Faculty, Karamanoglu Mehmetbey University, 70100 Karaman, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esra","family":"Aslan","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Afyonkarahisar Health Sciences University, 03200 Afyonkarahisar, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bet\u00fcl Demirciler","family":"Yava\u015f","sequence":"additional","affiliation":[{"name":"Private Practice, Traditional and Complementary Treatment Center, 03200 Afyonkarahisar, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0055-7688","authenticated-orcid":false,"given":"Mehmet Bilgehan","family":"Pekta\u015f","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine, Afyonkarahisar Health Sciences University, 03200 Afyonkarahisar, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Can-cer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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