Seung-Chan An, Hak Hoon Jun, Kyeong Mi Kim, Issac Kim, Sujin Choi, Hyunjeong Yeo, Soonchul Lee, Hyun-Ju An
{"title":"奥拉诺芬作为治疗甲状腺无节细胞癌的新型抗癌药物","authors":"Seung-Chan An, Hak Hoon Jun, Kyeong Mi Kim, Issac Kim, Sujin Choi, Hyunjeong Yeo, Soonchul Lee, Hyun-Ju An","doi":"10.3390/ph17101394","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background/Objectives:</b> Anaplastic thyroid cancer (ATC) is an aggressive and rare cancer with a poor prognosis, and traditional therapies have limited efficacy. This study investigates drug repositioning, focusing on auranofin, a gold-based drug originally used for rheumatoid arthritis, as a potential treatment for ATC. <b>Methods:</b> Auranofin was identified from an FDA-approved drug library and tested on two thyroid cancer cell lines, 8505C and FRO. Antitumor efficacy was evaluated through gene and protein expression analysis using Western blot, FACS, and mRNA sequencing. In vivo experiments were conducted using subcutaneous injections in nude mice to confirm the anticancer effects of auranofin. <b>Results:</b> Auranofin induced reactive oxygen species (ROS) production and apoptosis, leading to a dose-dependent reduction in cell viability, G1/S phase cell cycle arrest, and altered expression of regulatory proteins. It also inhibited cancer stem cell activity and suppressed epithelial-mesenchymal transition. mRNA sequencing revealed significant changes in the extracellular matrix-receptor interaction pathway, supported by Western blot results. In vivo xenograft models demonstrated strong antitumor activity. <b>Conclusions:</b> Auranofin shows promise as a repurposed therapeutic agent for ATC, effectively inhibiting cell proliferation, reducing metastasis, and promoting apoptosis. These findings suggest that auranofin could play a key role in future ATC treatment strategies.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 10","pages":""},"PeriodicalIF":4.3000,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510098/pdf/","citationCount":"0","resultStr":"{\"title\":\"Auranofin as a Novel Anticancer Drug for Anaplastic Thyroid Cancer.\",\"authors\":\"Seung-Chan An, Hak Hoon Jun, Kyeong Mi Kim, Issac Kim, Sujin Choi, Hyunjeong Yeo, Soonchul Lee, Hyun-Ju An\",\"doi\":\"10.3390/ph17101394\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Background/Objectives:</b> Anaplastic thyroid cancer (ATC) is an aggressive and rare cancer with a poor prognosis, and traditional therapies have limited efficacy. This study investigates drug repositioning, focusing on auranofin, a gold-based drug originally used for rheumatoid arthritis, as a potential treatment for ATC. <b>Methods:</b> Auranofin was identified from an FDA-approved drug library and tested on two thyroid cancer cell lines, 8505C and FRO. Antitumor efficacy was evaluated through gene and protein expression analysis using Western blot, FACS, and mRNA sequencing. In vivo experiments were conducted using subcutaneous injections in nude mice to confirm the anticancer effects of auranofin. <b>Results:</b> Auranofin induced reactive oxygen species (ROS) production and apoptosis, leading to a dose-dependent reduction in cell viability, G1/S phase cell cycle arrest, and altered expression of regulatory proteins. It also inhibited cancer stem cell activity and suppressed epithelial-mesenchymal transition. mRNA sequencing revealed significant changes in the extracellular matrix-receptor interaction pathway, supported by Western blot results. In vivo xenograft models demonstrated strong antitumor activity. <b>Conclusions:</b> Auranofin shows promise as a repurposed therapeutic agent for ATC, effectively inhibiting cell proliferation, reducing metastasis, and promoting apoptosis. These findings suggest that auranofin could play a key role in future ATC treatment strategies.</p>\",\"PeriodicalId\":20198,\"journal\":{\"name\":\"Pharmaceuticals\",\"volume\":\"17 10\",\"pages\":\"\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-10-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510098/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmaceuticals\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3390/ph17101394\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceuticals","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/ph17101394","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Auranofin as a Novel Anticancer Drug for Anaplastic Thyroid Cancer.
Background/Objectives: Anaplastic thyroid cancer (ATC) is an aggressive and rare cancer with a poor prognosis, and traditional therapies have limited efficacy. This study investigates drug repositioning, focusing on auranofin, a gold-based drug originally used for rheumatoid arthritis, as a potential treatment for ATC. Methods: Auranofin was identified from an FDA-approved drug library and tested on two thyroid cancer cell lines, 8505C and FRO. Antitumor efficacy was evaluated through gene and protein expression analysis using Western blot, FACS, and mRNA sequencing. In vivo experiments were conducted using subcutaneous injections in nude mice to confirm the anticancer effects of auranofin. Results: Auranofin induced reactive oxygen species (ROS) production and apoptosis, leading to a dose-dependent reduction in cell viability, G1/S phase cell cycle arrest, and altered expression of regulatory proteins. It also inhibited cancer stem cell activity and suppressed epithelial-mesenchymal transition. mRNA sequencing revealed significant changes in the extracellular matrix-receptor interaction pathway, supported by Western blot results. In vivo xenograft models demonstrated strong antitumor activity. Conclusions: Auranofin shows promise as a repurposed therapeutic agent for ATC, effectively inhibiting cell proliferation, reducing metastasis, and promoting apoptosis. These findings suggest that auranofin could play a key role in future ATC treatment strategies.
PharmaceuticalsPharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.10
自引率
4.30%
发文量
1332
审稿时长
6 weeks
期刊介绍:
Pharmaceuticals (ISSN 1424-8247) is an international scientific journal of medicinal chemistry and related drug sciences.Our aim is to publish updated reviews as well as research articles with comprehensive theoretical and experimental details. Short communications are also accepted; therefore, there is no restriction on the maximum length of the papers.