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Apoptosis

, Volume 15, Issue 5, pp 574–585 | Cite as

Curcumin sensitizes non-small cell lung cancer cell anoikis through reactive oxygen species-mediated Bcl-2 downregulation

  • Varisa Pongrakhananon
  • Ubonthip Nimmannit
  • Sudjit Luanpitpong
  • Yon Rojanasakul
  • Pithi Chanvorachote
Original Paper

Abstract

Anoikis, an apoptosis triggered by loss of cell anchorage, has been shown to be a principal mechanism of inhibition of tumor metastasis. Recently, anti-apoptotic Bcl-2 and Cav-1 proteins have been demonstrated to be highly associated with tumor metastasis and apoptosis resistance. Curcumin, a major active component of turmeric, Curcuma longa, has been shown to inhibit neoplastic evolution and tumor progression; however, the underlying mechanisms are unclear. In this study, we investigated the effect of curcumin on cell anoikis as a possible mechanism of anti-tumorigenic action of curcumin, and evaluated the potential role of Bcl-2 and Cav-1 in this process. Our results showed that ectopic expression of either Bcl-2 or Cav-1 induced anoikis resistance of lung carcinoma H460 cells. Curcumin downregulated Bcl-2 protein during anoikis and sensitized the cells to detachment-induced apoptosis, whereas it had no significant effect on Cav-1 protein expression. Bcl-2 down-regulation as well as anoikis enhancement by curcumin were inhibited by superoxide anion scavenger, Mn(III)tetrakis(4-benzoic acid) porphyrin chloride, but were unaffected by other ROS scavengers including catalase and deferoxamine, suggesting that superoxide anion is a key player in the downregulation of Bcl-2 by curcumin. Furthermore, we provided evidence that curcumin decreased Bcl-2 level through ubiquitin-proteasomal degradation which sensitized cells to detachment-induced apoptosis. These findings indicate a novel pathway for curcumin regulation of Bcl-2 and provide a key mechanism of anoikis regulation that may be exploited for metastatic cancer treatment.

Keywords

Curcumin Anoikis Superoxide anion Bcl-2 Caveolin-1 

Abbreviations

XTT

2,3-Bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5 carboxanilide inner salt

DHE

Dihydroethidium

H2DCF-DA

Dihydrodichlorofluorescein diacetate

MnTBAP

Mn(III)tetrakis(4-benzoic acid) porphyrin chloride

Def

Deferoxamine

Cat

Catalase

polyHEMA

Poly(2-hydroxy ethylmethacrylate)

Cav-1

Caveolin-1

Notes

Acknowledgments

This work was supported by the Thailand Research Fund (MG5080134; Pithi Chanvorachote and RGJ 5.Q.CU/50/A.1).

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Varisa Pongrakhananon
    • 1
  • Ubonthip Nimmannit
    • 2
  • Sudjit Luanpitpong
    • 1
  • Yon Rojanasakul
    • 3
  • Pithi Chanvorachote
    • 4
  1. 1.Pharmaceutical Technology (International) ProgramChulalongkorn UniversityBangkokThailand
  2. 2.National Nanotechnology CenterPathumthaniThailand
  3. 3.Department of Pharmaceutical SciencesWest Virginia UniversityMorgantownUSA
  4. 4.Department of Pharmacology and PhysiologyChulalongkorn UniversityBangkokThailand

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