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Moshnikova AB Afanasyev VN Proussakova OV Chernyshov S Gogvadze V Beletsky IP 《Cellular and molecular life sciences : CMLS》2006,63(2):229-234
Currently, chemical bifunctional cross-linkers are regarded as promising therapeutic agents capable of affecting cell metabolism.
Depending on the nature of the active groups and on the length of their mediating spacer, these cross-linkers have been shown
to influence mitochondrial functions, the cell cycle and cell death. The current study was aimed to assay cellular effects
of a cross-linker with ‘zero’-length spacer, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). When added to cultures
of transformed cells, EDC induced a G2/M blockade followed by cell death. Analysis of the molecular targets revealed that
alteration of the cell cycle was caused by EDC-induced interchain cross-linking within double-stranded DNA. Administration
of EDC to animals with experimental tumors increased their life span. The analysis of tumor cells from EDC-treated mice showed
up-regulation of p21/WAF1, disturbance of tumor cell cytokinesis and, hence, cell death. Thus, both in vitro and in vivo, EDC exhibits cytotoxic activity, which may be of potential therapeutic use.
Received 15 August 2005; received after revision 23 September 2005; accepted 15 November 2005 相似文献
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