| Induction of apoptosis of human B-CLL and ALL cells by a novel retinoid and its nonretinoidal analog. | |
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MedLine Citation:
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PMID: 12351403 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have recently described a novel retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic acid (CD437/AHPN) that induces apoptosis in a number of malignant cell types. We now describe our studies examining the effects of CD437 and a nonretinoidal analog (MM002) on the in vitro proliferation of the ALL-REH cell line, the in vitro and in vivo growth of a novel Epstein-Barr virus-negative (EBV(-)) B-cell chronic lymphocytic leukemia (B-CLL) cell line (WSU-CLL), and primary cultures of human B-CLL and acute lymphoblastic leukemia (ALL) cells. CD437 and MM002 induce apoptosis in both cell lines, as indicated by the activation of caspase-2 and caspase-3, cleavage of poly(adenosine diphosphate-ribose) (poly(ADP-ribose)) polymerase, increase in annexin V binding, and subsequent nuclear fragmentation. CD437-mediated apoptosis was not associated with the modulation of Bcl-2, Bax, or Mcl-1 levels, but was associated with the cleavage of the antiapoptotic protein Bcl-X(L) to a proapoptotic 18-kD form. This cleavage of Bcl-X(L) was dependent on caspase-3 activation since Bcl-X(L) cleavage and apoptosis were inhibited by the caspase-3 inhibitor Z-DVED-fmk. CD437 markedly inhibited the growth of WSU-CLL cells in severe combined immunodeficiency (SCID) mice. Tumor growth inhibition, growth delay, and log cell kill were 85.7%, 21 days, and 2.1, respectively, in the treated mice. Moreover, 1 of the 5 treated mice was tumor-free longer than 150 days and thus was considered cured. Exposure of primary cultures of both B-CLL and ALL cells obtained from patients to CD437 and MM002 resulted in their apoptosis. These results suggest that CD437 and MM002 analogs may have a potential role in the treatment of B-CLL and ALL. |
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Authors:
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Yuxiang Zhang; Marcia I Dawson; Ramzi Mohammad; Arun K Rishi; Lulu Farhana; Kai-Chia Feng; Mark Leid; Valerie Peterson; Xiao-Kun Zhang; Mark Edelstein; David Eilander; Sandra Biggar; Nathan Wall; Uwe Reichert; Joseph A Fontana |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Blood Volume: 100 ISSN: 0006-4971 ISO Abbreviation: Blood Publication Date: 2002 Oct |
Date Detail:
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Created Date: 2002-09-27 Completed Date: 2002-12-05 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 2917-25 Citation Subset: AIM; IM |
Affiliation:
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Department of Medicine, Karmanos Cancer Institute, Wayne State University, and the John D Dingell VA Medical Center, Detroit, MI 48201, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetylation Antineoplastic Agents / pharmacokinetics, toxicity* Apoptosis / drug effects Cell Division / drug effects Dose-Response Relationship, Drug Esters Humans Hydrolysis Kinetics Leukemia, Lymphocytic, Chronic, B-Cell / pathology* Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology* Retinoids / pharmacokinetics, toxicity* Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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P01 CA51993/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/CD 437; 0/Esters; 0/Retinoids |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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