Document Detail

Evodiamine induces tumor cell death through different pathways: apoptosis and necrosis.
MedLine Citation:
PMID:  14704127     Owner:  NLM     Status:  MEDLINE    
AIM: To study the different death pathways in human cervical cancer HeLa and melanoma A375-S2 cells initiated by evodiamine. METHODS: Viability of evodiamine-induced HeLa and A375-S2 cells was measured by MTT assay. Apoptotic cells with condensed or fragmented nuclei were visualized by Hoechst 33258 staining. Nucleosomal DNA fragmentation was assayed by agarose gel electrophoresis. Proportion of cell death through apoptotic and necrotic pathways was determined by LDH activity-based cytotoxicity assays. Cell cycle distribution was observed by flow cytometry. RESULTS: Evodiamine induced HeLa and A375-S2 cell death dose- and time-dependently. Caspase-3 and -8 were activated in apoptosis induced by evodiamine 15 micromol/L. However, over 24-h incubation of A375-S2 cells, evodiamine 15 micromol/L initiated necrosis related to p38 and ERK (extracellular signal-regulated kinases) activities. Evodiamine-induced HeLa cell death was preceded by an accumulation of cells at the G2/M phase of the cell cycle, but there was no significant effect of evodiamine on A375-S2 cell cycle. CONCLUSION: Evodiamine induces caspase-3,8-dependent apoptosis in HeLa cells which is related to G2/M arrest of the cell cycle. On the other hand, in A375-S2 cells, evodiamine initiates caspase-3,8-mediated apoptosis at early stages and the induction of MAPK-mediated necrosis at later stages of cell culture.
Ying Zhang; Li-Jun Wu; Shin-Ichi Tashiro; Satoshi Onodera; Takashi Ikejima
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Acta pharmacologica Sinica     Volume:  25     ISSN:  1671-4083     ISO Abbreviation:  Acta Pharmacol. Sin.     Publication Date:  2004 Jan 
Date Detail:
Created Date:  2004-01-05     Completed Date:  2004-08-20     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100956087     Medline TA:  Acta Pharmacol Sin     Country:  China    
Other Details:
Languages:  eng     Pagination:  83-9     Citation Subset:  IM    
China-Japan Research Institute of Medical and Pharmaceutical Sciences; Shenyang Pharmaceutical University, Shenyang 110016, China.
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MeSH Terms
Apoptosis / drug effects*
Caspase 3
Caspase 8
Caspases / metabolism*
Cell Cycle
DNA Fragmentation
Dose-Response Relationship, Drug
Evodia / chemistry
Hela Cells / metabolism,  pathology
Melanoma / metabolism,  pathology
Mitogen-Activated Protein Kinases / metabolism*
Plant Extracts / administration & dosage,  isolation & purification,  pharmacology*
Plants, Medicinal / chemistry
Quinazolines / administration & dosage,  isolation & purification,  pharmacology*
Time Factors
p38 Mitogen-Activated Protein Kinases
Reg. No./Substance:
0/Plant Extracts; 0/Quinazolines; 5956-87-6/evodiamine; EC Protein Kinases; EC Mitogen-Activated Protein Kinases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/CASP8 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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