Document Detail


Metformin potentiates the anticancer effects of cisplatin under normoxic conditions in vitro.
MedLine Citation:
PMID:  25421433     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Metformin is a diabetes drug with anticancer properties. Several studies have investigated the effects of metformin combined with chemotherapeutic agents, with controversial results. This study evaluated the efficacy of combined metformin/cisplatin treatment in an endometrial cancer cell line. Ishikawa cells were treated with metformin, cisplatin or both types of treatment. Cell proliferation was evaluated by quantification and colorimetric and thymidine incorporation assays, cell cycle progression was assessed by flow cytometry, and apoptosis by the caspase-3 activity assay. The effects of metformin and cisplatin used in combination were assessed under normoxic (21% O2) and hypoxic (1% O2) conditions. Mitochondrial morphology was examined using the MitoTracker dye, while function was assayed by lactate production. Discrepant results were obtained from the different assays of cell proliferation, with the value obtained from the colorimetric assay being higher than that from cell counts after drug treatment. Combined treatment with metformin (≥2 mM) and cisplatin (1 µM) had additive anti-proliferative effects on cells under normoxic conditions. However, the additive effect of metformin was attenuated under hypoxia. Metformin caused morphological and functional changes in mitochondria, which appeared shortened after exposure to metformin, while the connections between individual mitochondria appeared weaker. Additionally, decreased MitoTracker staining was observed after an 8-h exposure to metformin. The colorimetric assay did not accurately determine the effects of metformin and cisplatin on cell proliferation. The additive effects of metformin on cisplatin-induced inhibition of cell proliferation were attenuated under hypoxic conditions, while metformin compromised mitochondrial structure and function. Additional studies are needed to determine the efficacy of this drug combination in vivo.
Authors:
Takashi Uehara; Akira Mitsuhashi; Nobuhide Tsuruoka; Makio Shozu
Related Documents :
8314333 - Activation of the protein kinase a signal transduction pathway by granulocyte-macrophag...
25441423 - Synergistic effect of curcumin on epigallocatechin gallate-induced anticancer action in...
14723683 - Peptidase activity in various species of dairy thermophilic lactobacilli.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-21
Journal Detail:
Title:  Oncology reports     Volume:  -     ISSN:  1791-2431     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-25     Completed Date:  -     Revised Date:  2014-11-26    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

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


Previous Document:  Calcium silicate cement-induced remineralisation of totally demineralised dentine in comparison with...
Next Document:  MitoCOGs: clusters of orthologous genes from mitochondria and implications for the evolution of euka...