Format

Send to

Choose Destination
Apoptosis. 2008 Jul;13(7):904-14. doi: 10.1007/s10495-008-0221-x.

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

Author information

1
Terra Linda High School, 320 Nova Albion Way, San Rafael, CA 94903, USA.

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 Ca(2+) by inhibiting the Ca(2+)-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.

PMID:
18493855
PMCID:
PMC2727483
DOI:
10.1007/s10495-008-0221-x
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center