Coupling endoplasmic reticulum stress to the cell death program in mouse melanoma cells: effect of curcumin |
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Authors: | Jason Bakhshi Lee Weinstein Karen S Poksay Brian Nishinaga Dale E Bredesen Rammohan V Rao |
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Institution: | (1) Terra Linda High School, 320 Nova Albion Way, San Rafael, CA 94903, USA;(2) Undergraduate Program, University of California, 2200 University Ave, Berkeley, CA 94720, USA;(3) The Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA 94945, USA;(4) Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA;(5) University of California, San Francisco, CA 94143, USA |
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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. |
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Keywords: | Endoplasmic reticulum Curcumin ER stress Caspase Apoptosis Programmed cell death |
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