| Melittin induces Bcl-2 and caspase-3-dependent apoptosis through downregulation of Akt phosphorylation in human leukemic U937 cells. | |
| | |
MedLine Citation:
|
PMID: 17936321 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Melittin (MEL), a major polypeptide in bee venom (BV), is known to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in MEL-induced apoptosis have not been fully elucidated, especially in human leukemic cells. In the present study, we report that MEL induces apoptosis in leukemic U937 cells through downregulating Akt signal pathways. Furthermore, MEL-induced apoptosis was accompanied by downregulation of Bcl-2 and activation of caspase-3. The induction of apoptosis also was accompanied by the downregulation of the inhibitor of apoptosis protein (IAP) family proteins. Treatment of U937 cells with the caspase-3 inhibitor, z-DEVD-fmk, was capable of significantly restoring cell viability in MEL-treated cells. Additionally, the caspase-3 mediated apoptotic response was significantly attenuated in Bcl-2-overexpressing U937 cells treated with MEL. These results indicate that downregulation of Bcl-2 plays a major role in activation of caspase-3 following MEL exposure. MEL also triggered downregulation of Akt. LY294002 (an inhibitor of Akt) significantly decreased cell viability and increased the proportion of cells with sub-G1 phase DNA content. The results indicated that key regulators in MEL-induced apoptosis in human leukemic U937 cells include Bcl-2 and caspase-3, which are controlled through the Akt signaling pathway. |
| | |
Authors:
|
Dong-Oh Moon; Sung-Yong Park; Yung Hyun Choi; Nam Deuk Kim; Chan Lee; Gi-Young Kim |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-09-02 |
Journal Detail:
|
Title: Toxicon : official journal of the International Society on Toxinology Volume: 51 ISSN: 0041-0101 ISO Abbreviation: Toxicon Publication Date: 2008 Jan |
Date Detail:
|
Created Date: 2008-01-14 Completed Date: 2008-03-26 Revised Date: 2009-11-19 |
Medline Journal Info:
|
Nlm Unique ID: 1307333 Medline TA: Toxicon Country: England |
Other Details:
|
Languages: eng Pagination: 112-20 Citation Subset: IM |
Affiliation:
|
Faculty of Applied Marine Science, Cheju National University, Jeju-si, Jeju Special Self-Governing Province 690-756, Republic of Korea. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Antineoplastic Agents
/
pharmacology Apoptosis / drug effects*, physiology Caspase 3 / metabolism* Cell Line, Tumor Cell Proliferation / drug effects Cell Survival / drug effects Down-Regulation Humans Melitten / pharmacology* Phosphorylation Proto-Oncogene Proteins c-akt / metabolism* Proto-Oncogene Proteins c-bcl-2 / metabolism* U937 Cells |
| Chemical | |
Reg. No./Substance:
|
0/Antineoplastic Agents; 0/Proto-Oncogene Proteins c-bcl-2; 20449-79-0/Melitten; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Arsenic-induced alteration in the expression of genes related to type 2 diabetes mellitus.
Next Document: Inhibition of Hep2 and HeLa cell proliferation in vitro and EAC tumor growth in vivo by Lapemis curt...