Potent effects of roniciclib alone and with sorafenib against well-differentiated thyroid cancer. Issue 10 (October 2018)

• Record Type: Journal Article
• Authors: Lin, Shu-Fu; Lin, Jen-Der; Hsueh, Chuen; Chou, Ting-Chao; Wong, Richard J
• Is Part Of: Endocrine-related cancer. Volume 25:Issue 10(2018)
• Page Start: 853
• Page End: 864
• Publication Date: 2018-10
• Subjects: roniciclib -- cyclin-dependent kinase -- well-differentiated thyroid cancer; Endocrine glands -- Cancer -- Periodicals; Endocrinology -- Periodicals; Cancer -- Endocrine aspects -- Periodicals; 616.9944005
• DOI: 10.1530/ERC-18-0150
• Languages: English
• ISSNs: 1351-0088

Abstract

Abstract : Activation of cyclin-dependent kinase activity is frequently observed in many human cancers; therefore, cyclin-dependent kinases that promote cell cycle transition and cell proliferation may be potential targets in the treatment of malignancy. The therapeutic effects of roniciclib, a cyclin-dependent kinase inhibitor for papillary and follicular thyroid cancer (designated as well-differentiated thyroid cancer), were investigated in this study. Roniciclib inhibited cell proliferation in two papillary and two follicular thyroid cancer cell lines in a dose-dependent manner. Roniciclib activated caspase-3 activity and induced apoptosis. Cell cycle progression was arrested in the G2/M phase. Roniciclib treatment in vivo retarded the growth of two well-differentiated thyroid tumors in xenograft models in a dose-dependent fashion. Furthermore, the combination of roniciclib with sorafenib was more effective than either single treatment in a follicular thyroid cancer xenograft model. Acceptable safety profiles appeared in animals treated with either roniciclib alone or roniciclib and sorafenib combination therapy. These findings support roniciclib as a potential drug for the treatment of patients with well-differentiated thyroid cancer.