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First published online February 25, 2015

Curcumin sensitizes human lung cancer cells to apoptosis and metastasis synergistically combined with carboplatin

Abstract

Although carboplatin is one of the standard chemotherapeutic agents for non-small cell lung cancer (NSCLC), it has limited therapeutic efficacy due to activation of a survival signaling pathway and the induction of multidrug resistance. Curcumin, a natural compound isolated from the plant Curcuma longa, is known to sensitize tumors to different chemotherapeutic agents. The aim of this study is to evaluate whether curcumin can chemosensitize lung cancer cells to carboplatin and to analyze the signaling pathway underlying this synergism. We investigated the synergistic effect of both agents on cell proliferation, apoptosis, invasion, migration, and expression of related signaling proteins using the human NSCLC cell line, A549. A549 cell was treated with different concentrations of curcumin and carboplatin alone and in combination. Combined treatment with curcumin and carboplatin inhibited tumor cell growth, migration, and invasion compared with either drug alone. Matrix metalloproteinase (MMP)-2 and MMP-9 were more efficiently downregulated by co-treatment than by each treatment alone. mRNA and protein expression of caspase-3 and caspase-9 and proapoptotic genes was increased in cells treated with a combination of curcumin and carboplatin, whereas expression of the antiapoptotic Bcl-2 gene was suppressed. Co-treatment of both agents substantially suppressed NF-κB activation and increased expression of p53. Phosphorylation of Akt, a protein upstream of NF-κB, was reduced, resulting in inhibition of the degradation of inhibitor of κB(IκBα), whereas the activity of extracellular signal-regulated kinase (ERK1/2) was enhanced. Our study demonstrated that the synergistic antitumor activity of curcumin combined with carboplatin is mediated by multiple mechanisms involving suppression of NF-κB via inhibition of the Akt/IKKα pathway and enhanced ERK1/2 activity. Based on this mechanism, curcumin has potential as a chemosensitizer for carboplatin in the treatment of patients with NSCLC.

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Published In

Article first published online: February 25, 2015
Issue published: November 2015

Keywords

  1. Curcumin
  2. carboplatin
  3. synergism
  4. lung neoplasm
  5. proliferation

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© 2015 by the Society for Experimental Biology and Medicine.

Authors

Affiliations

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea

Notes

Sang Haak Lee. Email: [email protected]

Authors’ Contributions

JHK and HSK managed the overall experiment and wrote the manuscript. HYL and IKK conducted the experiments and analyzed the data. JHH, CDY, and HHK participated in the interpretation of the studies and manuscript editing. HSM and SHL supervised the project. All authors read and approved the final manuscript. JHK and HSK contributed equally to this work.

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