Open AccessFlavopiridol causes cell cycle inhibition and demonstrates anti-cancer activity in anaplastic thyroid cancer models
Author(s) -
Nicole Pinto,
Stephenie D. Prokopec,
Farhad Ghasemi,
Jalna Meens,
Kara M. Ruicci,
Mohammed I. Khan,
Neil Mundi,
Krupal Patel,
Myung Woul Han,
John Yoo,
Kevin Fung,
Danielle MacNeil,
Joe S. Mymryk,
Alessandro Datti,
Paul C. Boutros,
Laurie Ailles,
Anthony C. Nichols
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0239315
Subject(s) - anaplastic thyroid cancer , in vivo , cell culture , cell cycle , cancer research , cancer , thyroid cancer , cell cycle checkpoint , cancer cell , cdk inhibitor , cell growth , in vitro , cyclin dependent kinase , chemistry , medicine , biology , biochemistry , genetics , microbiology and biotechnology
Anaplastic thyroid cancer (ATC) is a rare, but nearly uniformly fatal disease that is typically resistant to chemotherapy and radiation. Alternative strategies to target this cancer at a molecular level are necessary in order to improve dismal outcomes for ATC patients. We examined the effects of flavopiridol, a CDK inhibitor, in a panel of ATC cell lines. When cell lines were treated over a ten-point concentration range, CAL62, KMH2 and BHT-101 cell lines had a sub micromolar half-maximal inhibitory concentration, while no effect was seen in the non-cancerous cell line IMR-90. Flavopiridol treatment resulted in decreased levels of the cell cycle proteins CDK9 and MCL1, and induced cell cycle arrest. Flavopiridol also decreased the in vitro ability of ATC cells to form colonies and impeded migration using a transwell migration assay. In vivo , flavopiridol decreased tumor weight and tumor volume over time in a patient-derived xenograft model of ATC. Given the observed in vitro and in vivo activity, flavopiridol warrants further investigation for treatment of ATC.