Antineoplastic activity of a novel multimeric gemcitabine-monophosphate prodrug against thyroid cancer cells in vitro.

Abstract

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.

• Authors: R Kotchetkov, B Gröschel, W H Gmeiner, A A Krivtchik, E Trump, M Bitoova, J Cinatl, B Kornhuber, J Cinatl
• Journal: Anticancer research (Anticancer Res) 2000 Sep-Oct Vol. 20 Issue 5A Pg. 2915-22 ISSN: 0250-7005 [Print] Greece
• PMID: 11062701 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• FASLG protein, human
• Fas Ligand Protein
• Membrane Glycoproteins
• Prodrugs
• Proto-Oncogene Proteins c-bcl-2
• fas Receptor
• Deoxycytidine
• Gemcitabine

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Line
• Deoxycytidine (analogs & derivatives, chemistry, pharmacology)
• Fas Ligand Protein
• Humans
• Membrane Glycoproteins (biosynthesis)
• Molecular Structure
• Prodrugs (chemistry, pharmacology)
• Proto-Oncogene Proteins c-bcl-2 (biosynthesis)
• Thyroid Neoplasms (drug therapy)
• Tumor Cells, Cultured
• fas Receptor (biosynthesis)
• Gemcitabine