Authors: YongZhan Zhen YaJun Lin BoYang Shang YongSu Zhen
Publish Date: 2009/05/26
Volume: 90, Issue: 1, Pages: 44-51
Abstract
In the present study the effects of lidamycin LDM a member of the enediyne antibiotic family on two human multiple myeloma MM cell lines U266 and SKO007 were evaluated In MTS assay LDM showed much more potent cytotoxicity than conventional antiMM agents to both cell lines The IC50 values of LDM for the U266 and SKO007 cells were 00575 ± 00015 and 01585 ± 00166 nM respectively much lower than those of adriamycin dexamethasone and vincristine Mechanistically LDM triggered MM cells apoptosis by increasing the levels of cleaved poly ADPribose polymerase PARP and caspase3/7 In addition activation of p38 mitogenactivated protein kinase MAPK and cJun NH2terminal kinase JNK was a critical mediator in LDMinduced cell death Inhibition of the expression of p38 MAPK and JNK by pharmacological inhibitors reversed the LDMinduced apoptosis through decreasing the level of cleaved PARP and caspase3/7 Interestingly phosphorylation of extracellular signalrelated kinase was increased by LDM conversely MEK inhibitor synergistically enhanced LDMinduced cytotoxicity and apoptosis in MM cells The results demonstrated that LDM suppresses MM cell growth through the activation of p38 MAPK and JNK with the potential to be developed as a chemotherapeutic agent for MM
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