Apoptosis

, 13:904 | Cite as

Coupling endoplasmic reticulum stress to the cell death program in mouse melanoma cells: effect of curcumin

  • Jason Bakhshi
  • Lee Weinstein
  • Karen S. Poksay
  • Brian Nishinaga
  • Dale E. Bredesen
  • Rammohan V. Rao
Original paper

Abstract

The microenvironment of cancerous cells includes endoplasmic reticulum (ER) stress the resistance to which is required for the survival and growth of tumors. Acute ER stress triggers the induction of a family of ER stress proteins that promotes survival and/or growth of the cancer cells, and also confers resistance to radiation and chemotherapy. Prolonged or severe ER stress, however, may ultimately overwhelm the cellular protective mechanisms, triggering cell death through specific programmed cell death (pcd) pathways. Thus, downregulation of the protective stress proteins may offer a new therapeutic approach to cancer treatment. In this regard, recent reports have demonstrated the roles of the phytochemical curcumin in the inhibition of proteasomal activity and triggering the accumulation of cytosolic Ca2+ by inhibiting the Ca2+-ATPase pump, both of which enhance ER stress. Using a mouse melanoma cell line, we investigated the possibility that curcumin may trigger ER stress leading to programmed cell death. Our studies demonstrate that curcumin triggers ER stress and the activation of specific cell death pathways that feature caspase cleavage and activation, p23 cleavage, and downregulation of the anti-apoptotic Mcl-1 protein.

Keywords

Endoplasmic reticulum Curcumin ER stress Caspase Apoptosis Programmed cell death 

Abbreviations

ER

Endoplasmic reticulum

pcd

Programmed cell death

eIF2α

Eukaryotic initiation factor-2 alpha

GRP

Glucose regulated protein

Notes

Acknowledgements

We thank members of the Bredesen laboratory for helpful comments and discussions and Molly Susag for administrative assistance. This work was supported by grants from the National Institutes of Health (NS33376 to D.E.B. & R.V.R, AG12282 and NS45093 to D.E.B) and Elisabeth R. Levy and Family Foundation award.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Jason Bakhshi
    • 1
  • Lee Weinstein
    • 2
  • Karen S. Poksay
    • 3
  • Brian Nishinaga
    • 4
  • Dale E. Bredesen
    • 3
    • 5
  • Rammohan V. Rao
    • 3
  1. 1.Terra Linda High SchoolSan RafaelUSA
  2. 2.Undergraduate Program, University of CaliforniaBerkeleyUSA
  3. 3.The Buck Institute for Age ResearchNovatoUSA
  4. 4.Albert Einstein College of MedicineBronxUSA
  5. 5.University of CaliforniaSan FranciscoUSA

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