The effect of the combined action of roscovitine and Paclitaxel on the apoptotic and cell cycle regulatory mechanisms in colon and anaplastic thyroid cancer cells.

V V Pushkarev,M D Tronko,O I Kovzun,V M Pushkarev

doi:10.5402/2012/826305

Abstract

Aim. To study the significance of cyclin-dependent kinases (Cdks) in paclitaxel-dependent apoptosis in colon and undifferentiated thyroid cancer cells. Materials and Methods. Experiments were performed on undifferentiated thyroid carcinoma (KTC-2) and colon carcinoma (ARO) cell lines. Cells were treated with paclitaxel (Ptx) and inhibitor of Cdk, roscovitine. Cell survival test and Western blotting were used for characterization of the effects of paclitaxel and roscovitine on cancer cells. Results. It was shown that not c-Jun N-terminal kinase, but cyclin-dependent kinases are responsible for antiapoptotic Bcl-2 phosphorylation. Cdk inhibition enhanced the cytotoxic effects of Ptx at low drug concentrations. There was antagonism between Ptx and roscovitine at higher (25 nM) paclitaxel concentrations. Conclusion. Using of paclitaxel at low (2.5 to 5 nM) concentrations and roscovitine is a promising combination for further preclinical trials for the development of new therapeutic approaches to the treatment of colon and anaplastic thyroid cancer.

Highlights

Compounds that stabilize microtubules (MSA), which include taxanes, are effective anticancer drugs
cyclin-dependent kinases (Cdks) are serine/threonine kinases that play a key role in regulating both cell cycle and transcription through the phosphorylation of transcription factors and tumor suppressor proteins involved in DNA replication and cell division [2]
The aim of this study was to establish a connection between the effect of paclitaxel on cell cycle and induction of apoptotic processes in colon (CC) and anaplastic thyroid cancer (ATC) cell lines ARO and KTC-2

Summary

Research Article

Aim. To study the significance of cyclin-dependent kinases (Cdks) in paclitaxel-dependent apoptosis in colon and undifferentiated thyroid cancer cells. Experiments were performed on undifferentiated thyroid carcinoma (KTC-2) and colon carcinoma (ARO) cell lines. Cells were treated with paclitaxel (Ptx) and inhibitor of Cdk, roscovitine. Cell survival test and Western blotting were used for characterization of the effects of paclitaxel and roscovitine on cancer cells. Cdk inhibition enhanced the cytotoxic effects of Ptx at low drug concentrations. There was antagonism between Ptx and roscovitine at higher (25 nM) paclitaxel concentrations. Using of paclitaxel at low (2.5 to 5 nM) concentrations and roscovitine is a promising combination for further preclinical trials for the development of new therapeutic approaches to the treatment of colon and anaplastic thyroid cancer

Introduction

Materials and Methods

ISRN Biochemistry

Results and Discussion