| Enhanced anti-tumor activity by the combination of the natural compounds (-)-epigallocatechin-3-gallate and luteolin: potential role of p53. | |
| | |
MedLine Citation:
|
PMID: 20826787 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Natural dietary agents have drawn a great deal of attention toward cancer prevention because of their wide safety margin. However, single agent intervention has failed to bring the expected outcome in clinical trials; therefore, combinations of chemopreventive agents are gaining increasingly popularity. In the present study, we investigated a combinatorial approach using two natural dietary polyphenols, luteolin and EGCG, and found that their combination at low doses (at which single agents induce minimal apoptosis) synergistically increased apoptosis (3-5-fold more than the additive level of apoptosis) in both head and neck and lung cancer cell lines. This combination also significantly inhibited growth of xenografted tumors in nude mice. The in vivo findings also were supported by significant inhibition of Ki-67 expression and increase in TUNEL-positive cells in xenografted tissues. Mechanistic studies revealed that the combination induced mitochondria-dependent apoptosis in some cell lines and mitochondria-independent apoptosis in others. Moreover, we found more efficient stabilization and ATM-dependent Ser(15) phosphorylation of p53 due to DNA damage by the combination, and ablation of p53 using shRNA strongly inhibited apoptosis as evidenced by decreased poly(ADP-ribose) polymerase and caspase-3 cleavage. In addition, we observed mitochondrial translocation of p53 after treatment with luteolin or the combination of EGCG and luteolin. Taken together, our results for the first time suggest that the combination of luteolin and EGCG has synergistic/additive growth inhibitory effects and provides an important rationale for future chemoprevention trials of head and neck and lung cancers. |
| | |
Authors:
|
A R M Ruhul Amin; Dongsheng Wang; Hongzheng Zhang; Shifang Peng; Hyung Ju C Shin; Johann C Brandes; Mourad Tighiouart; Fadlo R Khuri; Zhuo Georgia Chen; Dong M Shin |
Related Documents
:
|
11239967 - Differential sensitivity of murine myeloid fdc-p1 cells and apoptosis resistant mutant(... 10329737 - Activation of an mdm2-specific caspase by p53 in the absence of apoptosis. 20616497 - Iaspp: a novel protein involved in pituitary tumorigenesis? 8709247 - Adenovirus type 5 early region 4 is responsible for e1a-induced p53-independent apoptosis. 10495107 - Extracellular matrix degradation by metalloproteinases and central nervous system disea... 14505317 - Cytometric analysis of protein expression and apoptosis in human primary cells with a n... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-09-08 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Nov |
Date Detail:
|
Created Date: 2010-11-01 Completed Date: 2010-11-30 Revised Date: 2011-11-07 |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
|
Languages: eng Pagination: 34557-65 Citation Subset: IM |
Affiliation:
|
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, Georgia 30322, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Anticarcinogenic Agents / agonists, pharmacology* Apoptosis / drug effects Caspase 3 / metabolism Catechin / agonists, analogs & derivatives*, pharmacology Cell Cycle Proteins / pharmacology Cell Line, Tumor DNA Damage / drug effects DNA-Binding Proteins / pharmacology Drug Synergism Gene Expression Regulation, Neoplastic / drug effects Head and Neck Neoplasms / metabolism*, prevention & control* Humans Ki-67 Antigen / biosynthesis Luteolin / agonists, pharmacology* Mice Mice, Nude Mitochondria / metabolism Neoplasm Transplantation Phosphorylation / drug effects Protein Stability / drug effects Protein-Serine-Threonine Kinases / pharmacology Tumor Suppressor Protein p53 / metabolism* Tumor Suppressor Proteins / pharmacology Xenograft Model Antitumor Assays |
| Grant Support | |
ID/Acronym/Agency:
|
P50 CA128613/CA/NCI NIH HHS; R01 CA112643/CA/NCI NIH HHS; U01 CA101244/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Anticarcinogenic Agents; 0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/Ki-67 Antigen; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 0/Tumor Suppressor Proteins; 154-23-4/Catechin; 491-70-3/Luteolin; 989-51-5/epigallocatechin gallate; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/ataxia telangiectasia mutated protein; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Structural and mechanistic studies on Klebsiella pneumoniae 2-Oxo-4-hydroxy-4-carboxy-5-ureidoimidaz...
Next Document: Shallow boomerang-shaped influenza hemagglutinin G13A mutant structure promotes leaky membrane fusio...