Effects of roniciclib in preclinical models of anaplastic thyroid cancer

Abstract

Many human cancers have altered cyclin-dependent kinase activity. Inhibition of cyclin-dependent kinases may arrest cell cycle progression and represents an important strategy in the treatment of malignancies. We evaluated the therapeutic effects of roniciclib, a cyclin-dependent kinase inhibitor, as a treatment for anaplastic thyroid cancer. Roniciclib inhibited anaplastic thyroid cancer cell proliferation in a dose-dependent manner. Roniciclib activated caspase-3 activity and induced apoptosis. Cell cycle progression was arrested in G2/M phase. In vivo, the growth of anaplastic thyroid cancer xenograft tumors was retarded by roniciclib treatment without evidence of toxicity. These data provide a rationale for further clinical evaluation using roniciclib in the treatment of patients with anaplastic thyroid cancer.

Activity of roniciclib in medullary thyroid cancer

“…Our prior study revealed that roniciclib decreased survivin expression in anaplastic thyroid cancer tumors [ 28 ]. Survivin is a component of the chromosomal passenger complex that is involved in mitotic progression [ 29 – 31 ].…”

Therapeutic inhibition of polo‐like kinases in anaplastic thyroid cancer

“…Three human ATC cell lines, 8505C, 8305C, and KAT18, were evaluated in this study 24‐26 . Cell line identity was validated using DNA short tandem repeat profiling and cells were stored in liquid nitrogen until use.…”

Potent effects of roniciclib alone and with sorafenib against well-differentiated thyroid cancer

“…Apoptosis has an important role in cancer therapy (Galluzzi et al 2012). Roniciclib activates caspase-3 activity and induces apoptosis in HeLa and anaplastic thyroid cancer cell lines (Siemeister et al 2012, Lin et al 2017a. Therefore, we evaluated the effects of roniciclib on apoptosis in papillary and follicular thyroid cancer cell lines.…”

“…Roniciclib inhibits cell cycle transition, promotes caspase-3 activity and stimulates apoptosis in vitro. Oral administration of roniciclib has potent efficacy in impeding tumor growth of cervical, lung and anaplastic thyroid cancer xenografts, with favorable safety profiles in animal models (Siemeister et al 2012, Lin et al 2017a. The objective of this study was to evaluate the therapeutic effects of roniciclib in WDTC in vitro and in vivo.…”