Coadministration of Erlotinib and Curcumin Augmentatively Reduces Cell Viability in Lung Cancer Cells

Resistance to erlotinib in lung cancer cases includes T790M mutant epidermal growth factor receptor and c‐Met gene amplification, but other unknown mechanisms account for about 30% of the resistance. Activation of the nuclear factor kappa B (NFkappaB)‐related pathways in association with the reducti...

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Bibliographic Details
Published in:Phytotherapy research 2014-05, Vol.28 (5), p.728-735
Main Authors: Yamauchi, Yoshikane, Izumi, Yotaro, Yamamoto, Jun, Nomori, Hiroaki
Format: Article
Language:English
Subjects:
Animals
apoptosis
Apoptosis - drug effects
Cell Line, Tumor
Cell Survival - drug effects
cell viability
curcumin
Curcumin - pharmacology
epidermal growth factor
erlotinib
Erlotinib Hydrochloride
gene amplification
Humans
I-kappa B Proteins - metabolism
ikappaB
Lung cancer
lung neoplasms
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Transplantation
NFkappaB
Quinazolines - pharmacology
RNA Interference
small interfering RNA
transcription factor NF-kappa B
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Summary:Resistance to erlotinib in lung cancer cases includes T790M mutant epidermal growth factor receptor and c‐Met gene amplification, but other unknown mechanisms account for about 30% of the resistance. Activation of the nuclear factor kappa B (NFkappaB)‐related pathways in association with the reduction in ikappaB level may be one of such potential mechanisms. It is known that curcumin inhibits the inducible activation of NFkappaB at least in part by sustaining ikappaB expression level. Therefore, we evaluated the effects of coadministration of erlotinib and curcumin on lung cancer cells. We found that erlotinib and curcumin augmentatively reduced cell viability. Studies in PC9 cells showed that induction of apoptosis was involved. Expression of ikappaB was elevated in PC9 cells by curcumin administration, and pretreatment with siRNAs for ikappaB significantly attenuated the reduction in cell viability after coadministration of erlotinib and curcumin. Furthermore, coadministration of erlotinib and/or curcumin augmentatively attenuated the growth of PC9 tumors in mice. These results suggested the existence of an augmentative tumor growth inhibitory effect between erlotinib and curcumin, and this effect was at least in part mediated by the increase in the expression of ikappaB induced by curcumin. Copyright © 2013 John Wiley & Sons, Ltd.
ISSN:0951-418X
1099-1573
DOI:10.1002/ptr.5056