Curcumin: A Potent Candidate to be Evaluated as a Chemosensitizer in Paclitaxel Chemotherapy Against Cervical Cancer

  • Chanickal N. Sreekanth
  • Smitha V. Bava
  • Arun Kumar T. Thulasidasan
  • Nikhil P. Anto
  • Vino T. Cheriyan
  • Vineshkumar T. Puliyappadamba
  • Sajna G. Menon
  • Santhosh D. Ravichandran
  • Ruby John Anto
Conference paper

Abstract

Rigorous efforts in searching for novel chemosensitizers and unraveling their molecular mechanism have identified curcumin as one of the promising candidates. Our earlier report has shown that cervical cancer cells can be sensitized by curcumin to paclitaxel-induced apoptosis through down-regulation of NF-κB and Akt. The present study is an attempt to decipher the signaling pathways regulating the synergism of paclitaxel and curcumin and to determine whether the synergism exists in vivo. The study has clearly proved that Akt and NF-κB function successively in the sequence of paclitaxel-induced signaling events where Akt is up-stream of NF-κB. Inactivation of NF-κB did not affect the activation of Akt and survivin, while that of Akt significantly inhibited NF-κB and completely inhibited up-regulation of survivin. Up-regulation of cyclin-D1, COX-2, XIAP, and c-IAP1 and phosphorylation of MAPKs were completely inhibited on inactivation of NF-κB assigning a key regulatory role to NF-κB in the synergism. While up-regulation of survivin by paclitaxel is regulated by Akt, independent of NF-κB, inactivation of neither Akt nor NF-κB produced any change in Bcl-2 level suggesting a distinct pathway for its action. Mouse cervical multistage squamous cell carcinoma model using 3-methylcholanthrene and a xenograft model of human cervical cancer in NOD-SCID mice using HeLa cells were used to evaluate the synergism in vivo. The results suggest that curcumin augments the antitumor action of paclitaxel by down-regulating the activation and down-stream signaling of antiapoptotic factors and survival signals such as NF-κB, Akt, and MAPKs.

Keywords

Paclitaxel Curcumin NF-κB Akt MAPKs Synergism 

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Copyright information

© Springer India 2014

Authors and Affiliations

  • Chanickal N. Sreekanth
    • 1
  • Smitha V. Bava
    • 1
  • Arun Kumar T. Thulasidasan
    • 1
  • Nikhil P. Anto
    • 1
  • Vino T. Cheriyan
    • 1
  • Vineshkumar T. Puliyappadamba
    • 1
  • Sajna G. Menon
    • 1
  • Santhosh D. Ravichandran
    • 1
  • Ruby John Anto
    • 1
  1. 1.Integrated Cancer Research Program, Division of Cancer ResearchRajiv Gandhi Centre for BiotechnologyThiruvananthapuramIndia

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