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KMID : 0043320150380071351
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Archives of Pharmacal Research
2015 Volume.38 No. 7 p.1351 ~ p.1362
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Enhanced cell growth inhibition by thiacremonone in paclitaxel-treated lung cancer cells
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Ban Jung-Ok
Hwang Chul-Ju
Park Mi-Hee
Hwang In-Kook
Jeong Heon-Sang
Lee Hee-Pom
Hyun Byoung-Kook
Kim Ji-Young
Youn Hae-Suk
Ham Young-Wan
Yoon Do-Young
Han Sang-Bae
Song Min-Jong
Hong Jin-Tae
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Abstract
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Activation of nuclear factor kappa-B (NF-κB) is implicated in drug resistant of lung cancer cells. Our previous data showed that thiacremonone inhibited activation of NF-κB. In the present study, we investigated whether thiacremonone enhanced susceptibility of lung cancer cells to a common anti-cancer drug paclitaxel by further inhibition of NF-κB. Thus, we used the threefold lower doses of IC50 values (50 μg/ml thiacremonone and 2.5 nM paclitaxel). We found that combination treatment with thiacremonone and paclitaxel was more susceptible (combination index; 0.40 in NCI-H460 cells and 0.46 in A549 cells) in cell growth inhibition of two types of lung cancer cell lines compared to a single agent treatment. Consistent with the combination effect on cancer cell growth inhibition, the combination treatment further induced apoptotic cell death and arrested the cancer cells in G2/M phase accompanied with a much lower expression of cdc2 and cyclin B1, and inhibited colony formation. Much more inactivation of NF-κB and greater expression of NF-κB target apoptosis regulated genes such as caspase-8 and PARPs were found by the combination treatment. Molecular model and pull down assay as well as MALDI-TOF analysis demonstrated that thiacremonone directly binds to p50. These data indicated that thiacremonone leads to increased apoptotic cell death in lung cancer cell lines through greater inhibition of NF-κB by the combination treatment with paclitaxel.
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KEYWORD
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Thiacremonone, Paclitaxel, NF-kappaB, Apoptotic cell death, Lung cancer
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