Document Detail


The combination of arsenic and cryptotanshinone induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in breast cancer cells.
MedLine Citation:
PMID:  25412289     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Arsenic trioxide has been successfully used for the treatment of patients with acute promyelocytic leukemia (APL) worldwide. Recently, it has also been further developed to treat solid tumors in clinical trials. However, the therapeutic effects on malignant tumors appeared to be unsatisfactory, as these cells exhibited resistance towards arsenic. In this study, we explored new therapeutic strategies for treatment of human breast cancer MCF-7 cells based on arsenic metabolites. The MCF-7 cells were exposed to three arsenic species, namely, inorganic arsenite (iAs(III)) and its intermediate metabolites monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III)) either alone or in combination with cryptotanshinone (CPT) to establish their anticancer effects against MCF-7 cells. Surprisingly, MCF-7 cells were shown to be resistant to both iAs(III) and CPT when used alone; however, they were shown to be relatively sensitive to treatment when exposed to MMA(III) and DMA(III) alone. Conversely, the combination of MMA(III) with CPT showed significantly enhanced anticancer effects on MCF-7 cells at low doses, but no appreciable effect was observed upon exposure to the other two arsenic species with CPT. In addition, remarkable redistribution of pro-apoptosis related proteins Bax and Bak was observed in the mitochondria, together with activation of poly(ADP-ribose) polymerase (PARP) and caspase-9 after exposure to the combination of MMA(III) with CPT. Furthermore, we clearly found that induction of apoptosis in MCF-7 cells was predominantly triggered by endoplasmic reticulum (ER) stress after exposure to the combination of MMA(III) with CPT.
Authors:
Yan Fang Zhang; Min Zhang; Xu Lei Huang; Yu Jie Fu; Yu Han Jiang; Ling Ling Bao; Yasen Maimaitiyiming; Guang Ji Zhang; Qian Qian Wang; Hua Naranmandura
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-20
Journal Detail:
Title:  Metallomics : integrated biometal science     Volume:  -     ISSN:  1756-591X     ISO Abbreviation:  Metallomics     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-20     Completed Date:  -     Revised Date:  2014-11-21    
Medline Journal Info:
Nlm Unique ID:  101478346     Medline TA:  Metallomics     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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