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dc.contributor.authorAlqahtani, Tariq
dc.contributor.authorKumarasamy, Vishnu Muthuraj
dc.contributor.authorHuczyński, Adam
dc.contributor.authorSun, Daekyu
dc.date.accessioned2020-02-01T01:05:38Z
dc.date.available2020-02-01T01:05:38Z
dc.date.issued2019-11-20
dc.identifier.citationAlqahtani, T., Kumarasamy, V., Huczyński, A., & Sun, D. (2019). Salinomycin and its derivatives as potent RET transcriptional inhibitors for the treatment of medullary thyroid carcinoma. International Journal of Oncology. https://doi.org/10.3892/ijo.2019.4916 ‌en_US
dc.identifier.pmid31746350
dc.identifier.doi10.3892/ijo.2019.4916
dc.identifier.urihttp://hdl.handle.net/10150/636851
dc.description.abstractRearranged during transfection kinase (RET) is a validated molecular target in medullary thyroid cancer (MTC), as activating mutations in RET are often associated with the development of MTC. The present study reports the first preclinical characterization of salinomycin and selected analogs as potent RET transcriptional inhibitors. Reverse transcription‑PCR and immunoblotting revealed that salinomycin profoundly decreased RET expression in the TT human MTC cell line by inhibiting RET transcription. Moreover, salinomycin resulted in remarkable anti‑proliferative activity against MTC that is driven by RET (gain of function mutation) by selectively inhibiting the intracellular PI3K/Akt/mTOR signaling pathway. Also, flow cytometry and fluorescence‑activated cell sorting showed that salinomycin induces G1 phase arrest and apoptosis by reducing the expression of retinoblastoma protein, E2F1, cyclin D and CDK4. The structure‑activity relationship of salinomycin was investigated in this study. Some of the salinomycin derivatives showed the ability to reduce RET expression where others fail to alter RET expression. These results suggest that the RET‑suppressing effect of salinomycin may be largely attributed to disruption of the Wnt pathway, presumably through interference with the ternary LRP6‑Frizzled‑Wnt complex. Furthermore, these findings support the further preclinical evaluation of salinomycin and its analogs as a promising new class of therapeutic agents for the improved treatment of MTC.en_US
dc.description.sponsorshipAmerican Cancer Society [RSGM-12-046-01-CDD]en_US
dc.language.isoenen_US
dc.publisherSPANDIDOS PUBL LTDen_US
dc.rightsCOPYRIGHT 2020 Spandidos Publications.en_US
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectRETen_US
dc.subjectsalinomycinen_US
dc.subjectmedullary thyroid carcinomaen_US
dc.subjectWnt signalingen_US
dc.titleSalinomycin and its derivatives as potent RET transcriptional inhibitors for the treatment of medullary thyroid carcinomaen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Coll Pharm, Dept Pharmacol & Toxicolen_US
dc.contributor.departmentUniv Arizona, BIO5 Insten_US
dc.contributor.departmentUniv Arizona, Arizona Canc Ctren_US
dc.identifier.journalINTERNATIONAL JOURNAL OF ONCOLOGYen_US
dc.description.note6 month embargo; published online: 20 November 2019en_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitleInternational journal of oncology
dc.source.volume56
dc.source.issue1
dc.source.beginpage348
dc.source.endpage358
dc.source.countryGreece


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