Curcumin downregulates the constitutive activity of NF-kappaB and induces apoptosis in novel mouse melanoma cells.

Curcumin downregulates the constitutive activity of NF-kappaB and induces apoptosis in novel mouse melanoma cells. Research Abstract Details 

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Curcumin downregulates the constitutive activity of NF-kappaB and induces apoptosis in novel mouse melanoma cells. Abstract Text:

,Brian A Wall,Su Wang,Jin Namkoong,Jeffrey J Martino,Junghan Suh,Hwa Jin Lee,Arnold B Rabson,Chung S Yang,Suzie Chen,Jae-Ha Ryu,

Melanoma, the most deadly form of skin cancer, is very aggressive and resistant to present therapies. The transcription factor nuclear factor-kappa B (NF-kappaB) has been reported to be constitutively active in many types of cancer. Constitutively active NF-kappaB seen in melanoma likely plays a central role in cell survival and growth. We have established and characterized novel cell lines from our murine melanoma model. Here we report the constitutive activity of NF-kappaB in these melanoma-derived cells, as shown by electrophoretic mobility shift assay and reporter assays. We hypothesized that agents that inhibit NF-kappaB may also inhibit cell proliferation and may induce apoptosis in such melanoma cells. Curcumin has been shown to inhibit NF-kappaB activity in several cell types. In our system, curcumin selectively inhibited growth of melanoma cells, but not normal melanocytes. Curcumin induced melanoma cells to undergo apoptosis, as shown by caspase-3 activation, inversion of membrane phosphatidyl serine, and increases in cells in the sub-G1 phase. A curcumin dose-dependent inhibition of NF-kappaB-driven reporter activity correlated with decreased levels of phospho-IkappaBalpha, and decreased expression of NF-kappaB-target genes COX-2 and cyclin D1. This study demonstrates that the use of cells from our model system can facilitate studies of signaling pathways in melanoma. We furthermore conclude that curcumin, a natural and safe compound, inhibits NF-kappaB activity and the expression of its downstream target genes, and also selectively induces apoptosis of melanoma cells but not normal melanocytes. These encouraging in-vitro results support further investigation of curcumin for treatment of melanoma in vivo.

Curcumin downregulates the constitutive activity of NF-kappaB and induces apoptosis in novel mouse melanoma cells. Publishing Authors By Initials

YE ,BA Wall,S Wang,J Namkoong,JJ Martino,J Suh,HJ Lee,AB Rabson,CS Yang,S Chen,JH Ryu,

For similar cells: cells, cultured: tumor cells, cultured research abstracts see: cells: cells, cultured: tumor cells, cultured research

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Curcumin downregulates the constitutive activity of NF-kappaB and induces apoptosis in novel mouse melanoma cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Melanoma research

VOLUME: 17

Page Numbers: 274-83

Journal Abbreviation: Melanoma Res.

ISSN: 0960-8931

DAY: 19

MONTH: Oct

YEAR: 2007

Curcumin downregulates the constitutive activity of NF-kappaB and induces apoptosis in novel mouse melanoma cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9109623

Curcumin downregulates the constitutive activity of NF-kappaB and induces apoptosis in novel mouse melanoma cells. Keywords Mesh Terms:

KEYWORDS: Tumor Cells, Cultured

MESH TERMS: pathology

Chemical & Substance for Abstract: Curcumin downregulates the constitutive activity of NF-kappaB and induces apoptosis in novel mouse melanoma cells. Information

Substance Name: Caspase 3

Registry Number: EC 3.4.22.-

Grant and Affiliation Information for Curcumin downregulates the constitutive activity of NF-kappaB and induces apoptosis in novel mouse melanoma cells.

AFFILIATION: Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.

Country: England

AGENCY: United States NCI

GRANT: R01CA108720

ACRONYM: CA

MEDLINETA: Melanoma Res

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