Document Detail

Inhibition by arsenic trioxide of human hepatoma cell growth.
MedLine Citation:
PMID:  12065089     Owner:  NLM     Status:  MEDLINE    
Arsenic trioxide (As(2)O(3)) has been shown to be effective for treatment of patients with refractory or relapsed acute promyelocytic leukemia and a variety of other malignant hematopoetic disorders. We studied the effect of this agent on proliferation of human hepatoma-derived cell lines (SK-Hep-1, HepG2, and HuH7). In HuH7 cells, As(2)O(3) reduced proliferation time- and dose-dependently at 1 and 2 microM, while in SK-Hep-1 and HepG2 cells, As(2)O(3) inhibited proliferation at 2 and 4 microM respectively. Cell cycle analysis by flow cytometry showed that As(2)O(3) induced apoptosis in these hepatoma-derived cells as confirmed by appearance of sub-G(1) cells. Sensitivity of hepatoma-derived cells to As(2)O(3) was inversely related to their intracellular glutathione (GSH) and intensity of GSH synthesis. Arsenic sensitivity was restored to relatively resistant cell lines when GSH was depleted by L-buthionine sulfoximine (BSO). These results indicate that As(2)O(3) may have therapeutic potential for treatment of hepatocellular carcinoma.
Makoto Oketani; Kazunori Kohara; Demidmaa Tuvdendorj; Kenji Ishitsuka; Yasuji Komorizono; Kazuaki Ishibashi; Terukatsu Arima
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cancer letters     Volume:  183     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-06-14     Completed Date:  2002-09-25     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  147-53     Citation Subset:  IM    
The Second Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, Japan.
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MeSH Terms
Antineoplastic Agents / pharmacology
Arsenicals / pharmacology*
Carcinoma, Hepatocellular / prevention & control*
Cell Cycle
Cell Division / drug effects
Coloring Agents / pharmacology
Dose-Response Relationship, Drug
Flow Cytometry
Glutathione / metabolism
Oxides / pharmacology*
Tetrazolium Salts / pharmacology
Thiazoles / pharmacology
Time Factors
Tumor Cells, Cultured
Reg. No./Substance:
0/Antineoplastic Agents; 0/Arsenicals; 0/Coloring Agents; 0/Oxides; 0/Tetrazolium Salts; 0/Thiazoles; 1327-53-3/arsenic trioxide; 298-93-1/thiazolyl blue; 70-18-8/Glutathione

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