Abstract | BACKGROUND: METHODOLOGY/PRINCIPAL FINDINGS: In the present study we show that suppression of NF-κB activation by α- tomatine occurs through inhibition of I kappa B alpha (IκBα) kinase activity, leading to sequential suppression of IκBα phosphorylation, IκBα degradation, NF-κB/p65 phosphorylation, and NF-κB p50/p65 nuclear translocation. Consistent with its ability to induce apoptosis, α- tomatine reduced TNF-α induced activation of the pro-survival mediator Akt and its inhibition of NF-κB activation was accompanied by significant reduction in the expression of NF-κB-dependent anti-apoptotic (c-IAP1, c-IAP2, Bcl-2, Bcl-xL, XIAP and survivin) proteins. We also evaluated the antitumor activity of α- tomatine against PC-3 cell tumors grown subcutaneously and orthotopically in mice. Our data indicate that intraperitoneal administration of α- tomatine significantly attenuates the growth of PC-3 cell tumors grown at both sites. Analysis of tumor material indicates that the tumor suppressing effects of α- tomatine were accompanied by increased apoptosis and lower proliferation of tumor cells as well as reduced nuclear translocation of the p50 and p65 components of NF-κB. CONCLUSION/SIGNIFICANCE:
|
Authors | Sui-Ting Lee, Pooi-Fong Wong, Hui He, John David Hooper, Mohd Rais Mustafa |
Journal | PloS one
(PLoS One)
Vol. 8
Issue 2
Pg. e57708
( 2013)
ISSN: 1932-6203 [Electronic] United States |
PMID | 23437404
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antineoplastic Agents, Phytogenic
- Apoptosis Regulatory Proteins
- NF-kappa B
- Protein Subunits
- alpha-tomatine
- Tomatine
- I-kappa B Kinase
|
Topics |
- Adenocarcinoma
(drug therapy, genetics, metabolism, pathology)
- Animals
- Antineoplastic Agents, Phytogenic
(pharmacology)
- Apoptosis
(drug effects)
- Apoptosis Regulatory Proteins
(antagonists & inhibitors, genetics, metabolism)
- Cell Proliferation
(drug effects)
- Choristoma
- Gene Expression Regulation, Neoplastic
(drug effects)
- Humans
- I-kappa B Kinase
(antagonists & inhibitors, genetics, metabolism)
- Male
- Mice
- NF-kappa B
(antagonists & inhibitors, genetics, metabolism)
- Neoplasm Transplantation
- Phosphorylation
(drug effects)
- Prostatic Neoplasms
(drug therapy, genetics, metabolism, pathology)
- Protein Subunits
(antagonists & inhibitors, genetics, metabolism)
- Protein Transport
(drug effects)
- Signal Transduction
(drug effects)
- Tomatine
(analogs & derivatives, pharmacology)
|