Abstract:
:We have shown previously that EM011, a synthetic compound, binds tubulin with a higher affinity than the founding compound, noscapine, without changing total microtubule polymer mass. Now we show that EM011 is potently effective against vinblastine-resistant human lymphoblastoid line CEM/VLB100 and its parental vinblastine-sensitive line CEM. The cytotoxicity is mediated by cell cycle arrest at G2/M phase and subsequent apoptosis, as indicated by altered plasma membrane asymmetry, loss of mitochondrial transmembrane potential, activation of caspase-3, and increased DNA fragmentation. Furthermore, oral EM011 treatment of nude mice bearing human lymphoma xenografts results in pronounced tumor regression by triggering apoptosis and significantly lengthens the survival time of mice. EM011 treatment does not have obvious side effects in tissues with frequently dividing cells, such as the spleen and duodenum. In addition, EM011 does not show any toxicity in the liver, lung, heart, brain, and sciatic nerve. More importantly, EM011 does not affect hematopoiesis as determined by complete blood count profiles. These findings suggest that EM011 may be a safe and effective chemotherapeutic agent for oral treatment of drug-resistant human lymphomas.
journal_name
Bloodjournal_title
Bloodauthors
Aneja R,Zhou J,Vangapandu SN,Zhou B,Chandra R,Joshi HCdoi
10.1182/blood-2005-08-3516subject
Has Abstractpub_date
2006-03-15 00:00:00pages
2486-92issue
6eissn
0006-4971issn
1528-0020pii
2005-08-3516journal_volume
107pub_type
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