Curcumin synergistically augments bcr/abl phosphorothioate antisense oligonucleotides to inhibit growth of chronic myelogenous leukemia cells.
OBJECTIVE
To investigate the growth inhibition effect of the combination of bcr/abl phosphorothioate antisense oligonucleotides (PS-ASODN) and curcumin (cur), and the possible mechanisms of cur on the chronic myelogenous leukemia cell line K562.


METHODS
The K562 cell line was used as a P210( bcr/abl )-positive cell model in vitro and was exposed to different concentrations of PS-ASODN (0-20 micromol/L), cur (0-20 micromol/L), or a combination of both. Growth inhibition and apoptosis of K562 cells were assessed by MTT assay and AO/EB fluorescent staining, respectively. The expression levels of P210( bcr/abl ), NF-kappaB and heat shock protein 90 (Hsp90) were assessed by Western blot.


RESULTS
Exposure to cur (5-20 micromol/L) and PSASODN (5-20 micromol/L) resulted in a synergistic inhibitory effect on cell growth. Growth inhibition was associated with the inhibition of the proliferation and induction of apoptosis. Western blot analysis showed that the drugs synergistically downregulated the level of P210( bcr/abl ) and NF-kappaB. Cur downregulated Hsp90, whereas no synergism was observed when cur was combined with PS-ASODN.


CONCLUSIONS
PS-ASODN and cur exhibited a synergistic inhibitory effect on the cell growth of K562. The synergistic growth inhibition was mediated through different mechanisms that involved the inhibition of P210( bcr/abl ).
Zhang
Kun-Zhong
KZ
Institute of Clinical Pharmacology, School of Pharmacy, Fujian Medical University, Fujian 350004, China. xjh@mail.fjmu.edu.cn.
Xu
Jian-Hua
JH
Huang
Xiu-Wang
XW
Wu
Li-Xian
LX
Su
Yu
Y
Chen
Yuan-Zhong
YZ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D016328:NF-kappa B / Q000378:metabolism; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*
D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D016328:NF-kappa B; D020319:Oligodeoxyribonucleotides, Antisense; D016044:Fusion Proteins, bcr-abl; D003474:Curcumin