| Curcumin stimulates reactive oxygen species production and potentiates apoptosis induction by the antitumor drugs arsenic trioxide and lonidamine in human myeloid leukemia cell lines. | |
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MedLine Citation:
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PMID: 20605902 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Arsenic trioxide (ATO, Trisenox) is an important antileukemic drug, but its efficacy is frequently low when used as a single agent. Here, we demonstrate that the apoptotic action of ATO is greatly increased when combined with subcytotoxic curcumin concentrations in U937 and HL60 human acute myeloid leukemia cells, and with lower efficacy in K562 chronic myelogenous leukemia cells. Curcumin exerts similar cooperative effect with the mitochondria-targeting drug lonidamine, whereas the response is negligible in combination with the DNA-targeting drug cisplatin. Curcumin plus ATO or lonidamine stimulates typical events of the mitochondrial executioner pathway (Bax and Bid activation, cytochrome c release, X-linked inhibitor of apoptosis down-regulation, and caspase-9/-3 activation) and causes mitochondrial transmembrane potential dissipation, which nevertheless represents a late event in the apoptotic response. Curcumin increases anion superoxide production, and its proapoptotic action in combination with ATO and lonidamine is mimicked by pro-oxidant agents (2-methoxyestradiol and H(2)O(2)) and prevented by antioxidant agents [Mn(III)tetrakis(4-benzoic acid)porphyrin chloride and N-acetyl-l-cysteine]. Within the assayed time period (16-24 h), curcumin does not significantly modify p38-mitogen-activated protein kinase and c-Jun NH(2)-terminal kinase phosphorylation/activation or nuclear factor-κB activity, but it greatly stimulates extracellular signal-regulated kinase (ERK) phosphorylation, and decreases Akt phosphorylation. Experiments using mitogen-activated protein kinase kinase/ERK inhibitors [2'-amino-3'-methoxyflavone (PD98059) and 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene (U0126)] and phosphatidylinositol 3-kinase inhibitor 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) indicate that ERK activation does not mediate and even restrains apoptosis potentiation, whereas Akt down-regulation facilitates apoptosis generation. In summary, cotreatment with curcumin may represent a useful manner of increasing the efficacy of ATO and lonidamine as antitumor drugs in myeloid leukemia cells. |
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Authors:
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Yolanda Sánchez; Gloria P Simón; Eva Calviño; Elena de Blas; Patricio Aller |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-06 |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 335 ISSN: 1521-0103 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-21 Completed Date: 2010-10-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: United States |
Other Details:
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Languages: eng Pagination: 114-23 Citation Subset: IM |
Affiliation:
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Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Cientìficas, Madrid, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology* Apoptosis / drug effects* Apoptosis Regulatory Proteins / antagonists & inhibitors, biosynthesis Arsenicals / pharmacology* Blotting, Western Cell Survival / drug effects Curcumin / pharmacology* Electrophoretic Mobility Shift Assay Flow Cytometry Glutathione / metabolism HL-60 Cells Humans Indazoles / pharmacology* Membrane Potentials / drug effects Mitochondria / drug effects Oxidants / pharmacology Oxides / pharmacology* Protein Kinase Inhibitors / pharmacology Protein Kinases / metabolism Proto-Oncogene Proteins c-akt / biosynthesis, genetics Reactive Oxygen Species / metabolism* U937 Cells |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Apoptosis Regulatory Proteins; 0/Arsenicals; 0/Indazoles; 0/Oxidants; 0/Oxides; 0/Protein Kinase Inhibitors; 0/Reactive Oxygen Species; 1327-53-3/arsenic trioxide; 458-37-7/Curcumin; 50264-69-2/lonidamine; 70-18-8/Glutathione; EC 2.7.-/Protein Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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