The triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid and its derivatives elicit human lymphoid cell apoptosis through a novel pathway involving the unregulated mitochondrial permeability transition pore.

The triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid and its derivatives elicit human lymphoid cell apoptosis through a novel pathway involving the unregulated mitochondrial permeability transition pore. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

The triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid and its derivatives elicit human lymphoid cell apoptosis through a novel pathway involving the unregulated mitochondrial permeability transition pore. Abstract Text:

Paul S Brookes,Kimberly Morse,Denise Ray,Andrew Tompkins,Sara M Young,Shannon Hilchey,Suhail Salim,Marina Konopleva,Michael Andreeff,Richard Phipps,Steven H Bernstein,

2-Cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) and its C(28) imidazole and dinitrile derivatives are novel oleanane triterpenoids exhibiting promise as both therapeutic and preventative agents for cancer. Herein we show that these triterpenoids induce normal and malignant B-lymphoid cell apoptosis, with the C(28) derivatives being more potent than CDDO, through a novel mitochondrial mechanism. We show using both normal and malignant human B cells, as well as isolated rat mitochondria, that CDDO directly interacts with a limited number of as yet undefined mitochondrial proteins. Such an interaction results in the loss of mitochondrial thiol status and the secondary modification of numerous mitochondrial protein thiols. Our data further suggest that such modifications result in the formation of high molecular weight protein aggregates that form "unregulated," constitutively open, cyclosporin A-insensitive permeability transition (PT) pores. The formation of such PT pores results in the subsequent generation of mitochondrial superoxide and cell death. In total, our studies (a) suggest a novel mechanism of action for triterpenoid-induced cell death; (b) are among the first to directly support the existence of an unregulated PT pore formed by mitochondrial protein aggregates, as first proposed by Lemasters and colleagues; and (c) validate such an unregulated PT pore as a viable target for the development of new cancer therapeutics.

The triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid and its derivatives elicit human lymphoid cell apoptosis through a novel pathway involving the unregulated mitochondrial permeability transition pore. Publishing Authors By Initials

PS Brookes,K Morse,D Ray,A Tompkins,SM Young,S Hilchey,S Salim,M Konopleva,M Andreeff,R Phipps,SH Bernstein,

For similar inorganic chemicals: free radicals: reactive oxygen species research abstracts see: inorganic chemicals: free radicals: reactive oxygen species research

PUBMED ID PMID:

MEDLINE DATE:

The triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid and its derivatives elicit human lymphoid cell apoptosis through a novel pathway involving the unregulated mitochondrial permeability transition pore. Journal Published:

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

Journal: Cancer research

VOLUME: 67

Page Numbers: 1793-802

Journal Abbreviation: Cancer Res.

ISSN: 0008-5472

DAY: 15

MONTH: Feb

YEAR: 2007

The triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid and its derivatives elicit human lymphoid cell apoptosis through a novel pathway involving the unregulated mitochondrial permeability transition pore. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2984705

The triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid and its derivatives elicit human lymphoid cell apoptosis through a novel pathway involving the unregulated mitochondrial permeability transition pore. Keywords Mesh Terms:

KEYWORDS: Reactive Oxygen Species

MESH TERMS: metabolism

Chemical & Substance for Abstract: The triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid and its derivatives elicit human lymphoid cell apoptosis through a novel pathway involving the unregulated mitochondrial permeability transition pore. Information

Substance Name: Acetylcysteine

Registry Number: 616-91-1

Grant and Affiliation Information for The triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid and its derivatives elicit human lymphoid cell apoptosis through a novel pathway involving the unregulated mitochondrial permeability transition pore.

AFFILIATION: Department of Anesthesiology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: R01 HL 71158

ACRONYM: HL

MEDLINETA: Cancer Res

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

The triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid and its derivatives elicit human lymphoid cell apoptosis through a novel pathway involving the unregulated mitochondrial permeability transition pore Related Publications

• A population-based case-control study of CARD15 and other risk factors in Crohn's disease and ulcerative colitis.
• Alternative S2 hinge regions of the myosin rod differentially affect muscle function, myofibril dimensions and myosin tail length.
• Biochemical verification of smoking status in pregnant and recently postpartum women.
• Cholesterol lowering to prevent stroke: who, when, and how?
• Enhanced T-cell reconstitution by hematopoietic progenitors expanded ex vivo using the Notch ligand Delta1.
• Epigenetics: a landscape takes shape.
• Ethical guideposts to clinical trials in oncology.
• Follicular lymphoma intratumoral CD4+CD25+GITR+ regulatory T cells potently suppress CD3/CD28-costimulated autologous and allogeneic CD8+CD25- and CD4+CD25- T cells.
• HPLC measurement of ocular carotenoid levels in human donor eyes in the lutein supplementation era.
• High prevalence of aeroallergen sensitization among infants of atopic parents.
• Identification of 3-methoxyzeaxanthin as a novel age-related carotenoid metabolite in the human macula.
• Influence of dog ownership and high endotoxin on wheezing and atopy during infancy.
• Lexical and metrical stress in word recognition: lexical or pre-lexical influences?
• Long-term recreational physical activity and risk of invasive and in situ breast cancer: the California teachers study.
• Marijuana use motives: concurrent relations to frequency of past 30-day use and anxiety sensitivity among young adult marijuana smokers.
• Mice with enhanced macrophage angiotensin-converting enzyme are resistant to melanoma.
• Mold damage in homes and wheezing in infants.
• Nonfasting low-density lipoprotein testing: utility for cholesterol screening in pediatric primary care.
• Oral contraceptive use and risk of breast carcinoma in situ (United States).
• Perceived health moderates the association between smoking rate and panic vulnerability variables among daily smokers.
• Physical activity and colon cancer risk among women in the California Teachers Study.
• Production of deuterated lutein by Chlorella protothecoides and its detection by mass spectrometric methods.
• Quality of life in patients with brain tumor: what's relevant in our quest for therapeutic efficacy.
• RIX4414 (Rotarix): a live attenuated human rotavirus vaccine.
• Reversible cerebral vasoconstriction syndromes.
• Serum organochlorines and breast cancer: a case-control study among African-American women.
• Smoking status in the initial weeks of quitting as a predictor of smoking-cessation outcomes in pregnant women.
• The triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid and its derivatives elicit human lymphoid cell apoptosis through a novel pathway involving the unregulated mitochondrial permeability transition pore.
• Transcriptional regulation of the Drosophila melanogaster muscle myosin heavy-chain gene.
• Vertebrate and invertebrate carotenoid-binding proteins.