Document Detail


Antagonism between curcumin and the topoisomerase II inhibitor etoposide: a study of DNA damage, cell cycle regulation and death pathways.
MedLine Citation:
PMID:  22895066     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The use of combinations of chemotherapy and natural products has recently emerged as a new method of cancer therapy, relying on the capacity of certain natural compounds to trigger cell death with low doses of chemotherapeutic agents and few side effects. The current study aims to evaluate the modulatory effects of curcumin (CUR), Nigella sativa (NS) and taurine on etoposide (ETP) cytotoxicity in a panel of cancer cell lines and to identify their underlying mechanisms. CUR alone showed potent antitumor activity, but surprisingly, its interaction with ETP was antagonistic in four out of five cancer cell lines. Neither taurine nor Nigella sativa affect the sensitivity of cancer cells to ETP. Examination of the DNA damage response machinery (DDR) showed that both ETP and CUR elicited DNA double-strand breaks (DSB) and evoked γ-H2AX foci formation at doses as low as 1 µg/ml. Cell cycle analysis revealed S phase arrest after ETP or CUR application, whereas co-treatment with ETP and CUR led to increased arrest of the cell cycle in S phase (MCF-7 cells) or the accumulation of cells in G 2/M phases (HCT116, and HeLa cells). Furthermore, cotreatment with ETP and CUR resulted in modulation of the level of DNA damage induction and repair compared with either agent alone. Electron microscopic examination demonstrated that different modalities of cell death occurred with each treatment. CUR alone induced autophagy, apoptosis and necrosis, whereas ETP alone or in combination with CUR led to apoptosis and necrosis. Conclusions: Cotreatment with ETP and CUR resulted in an antagonistic interaction. This antagonism is related, in part, to the enhanced arrest of tumor cells in both S and G 2/M phases, which prevents the cells from entering M-phase with damaged DNA and, consequently, prevents cell death from occurring. This arrest allows time for the cells to repair DNA damage so that cell cycle -arrested cells can eventually resume cell cycle progression and continue their physiological program.
Authors:
Ekram M Saleh; Raafat A El-awady; Nadia A Eissa; Wael M Abdel-Rahman
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Publication Detail:
Type:  Journal Article     Date:  2012-08-16
Journal Detail:
Title:  Cancer biology & therapy     Volume:  13     ISSN:  1555-8576     ISO Abbreviation:  Cancer Biol. Ther.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-12     Completed Date:  2013-04-11     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  101137842     Medline TA:  Cancer Biol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1058-71     Citation Subset:  IM    
Affiliation:
Clinical Biochemistry and Molecular Biology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt. ekramsaleh@hotmail.com
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents, Phytogenic / pharmacology*
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Cell Cycle / drug effects*
Cell Death / drug effects
Cell Line, Tumor
Curcumin / pharmacology*
DNA Damage*
Drug Interactions
Etoposide / pharmacology*
HCT116 Cells
HeLa Cells
Hep G2 Cells
Humans
MCF-7 Cells
Taurine / pharmacology
Topoisomerase II Inhibitors / pharmacology*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Topoisomerase II Inhibitors; 107-35-7/Taurine; 33419-42-0/Etoposide; 458-37-7/Curcumin
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