Antineoplastic activity of a novel multimeric gemcitabine-monophosphate prodrug against thyroid cancer cells in vitro
Kotchetkov, R.; Gröschel, B.; Gmeiner, W.H.; Krivtchik, A.A.; Trump, E.; Bitoova, M.; Cinatl, J.; Kornhuber, B.; Cinatl, J.
Anticancer Research 20(5a): 2915-2922
2000
ISSN/ISBN: 0250-7005 PMID: 11062701 Document Number: 523054
Gemcitabine (Gem) is a deoxycytidine analog that is effective against pancreatic cancer and other malignancies following conversion to the 5'-O-mono-, di- and tri-phosphate forms. We evaluated the cytotoxicity of GemMP(10), a novel multimeric form of 2'-deoxy-2',2''-difluorocytidine-5'-O-monophosphate (gemcitabine monophosphate) against three thyroid carcinoma cell lines established from anaplastic (8505C), papillary (B-CPAP) and poorly-differentiated papillary (BHT-101) cancer. GemMP(10) decreased tumor cell growth at concentrations ranging from 1 to 50 nM. These concentrations were 5- to 10-fold lower than those required for inhibition of tumor cell growth by monomeric Gem. GemMP(10) cytotoxicity occurred via induction of apoptosis. Flow cytometric analysis of GemMP(10) treated cells revealed growth arrest in S-phase. Fas-antigen expression was increased in thyroid cancer cells treated with GemMP(10), whereas Fas-L and Bcl-2 expression were not significantly affected. These results demonstrated that GemMP(10) is a potent cytotoxic agent that serves to induce apoptosis in association with increased Fas expression in cultured thyroid cancer cell lines.