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 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.
Division of General Thoracic Surgery, Department of Surgery, School of Medicine, Keio University, Japan.
Yoshikane
Y
Yamauchi
Yotaro
Y
Izumi
Jun
J
Yamamoto
Hiroaki
H
Nomori
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology*; D000069347:Erlotinib Hydrochloride; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011799:Quinazolines / Q000494:pharmacology*; D034622:RNA Interference
D020672:I-kappa B Proteins; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D003474:Curcumin
NFkappaB; curcumin; erlotinib; ikappaB