Document Detail

Modulation of doxorubicin sensitivity by a novel organic compound, oxalyl bis (N-phenyl) hydroxamic acid on acetyl aminofluorene-induced preneoplastic hepatocytes.
MedLine Citation:
PMID:  14643023     Owner:  NLM     Status:  MEDLINE    
Development of biochemical modulators and application of the same with anticancer drugs is a current approach of modern cancer chemotherapy. We report the effect of two novel hydroxamic acid derivatives, viz. oxaly bis (N-phenyl) hydroxamic acid (OBPHA) and succinyl bis (N-phenyl) hydroxamic acid (SBPHA) on doxorubicin sensitivity and on P-glycoprotein (P-gp) in acetyl amino fluorene (AAF) induced preneoplastic hepatocytes in vitro. OBPHA increases doxorubicin sensitivity in AAF induced preneoplastic hepatocytes compared to normal hepatocytes. SBPHA, with an additional -CH(2)-CH(2)- group than OBPHA does not modulate the sensitivity of doxorubicin. The mechanism of action of OBPHA and SBPHA and their in vivo toxicity on male Swiss mice has been studied. OBPHA in combination with doxorubicin (i.e. OBPHA+doxorubicin) has higher antitumour activity compared to doxorubicin alone group; in consequence, OBPHA may decrease the dose related side effect of doxorubicin.
S K Choudhuri; Surajit Majumder
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer letters     Volume:  202     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2003-12-03     Completed Date:  2004-02-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  25-34     Citation Subset:  IM    
Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Calcutta 700026, India.
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MeSH Terms
2-Acetylaminofluorene / toxicity*
Antibiotics, Antineoplastic / therapeutic use*
Benzeneacetamides / therapeutic use*
Calcium Channel Blockers / pharmacology
Carcinogens / toxicity
Cell Division / drug effects
Dose-Response Relationship, Drug
Doxorubicin / therapeutic use*
Drug Synergism
Drug Therapy, Combination
Glutathione / metabolism
Hepatocytes / drug effects*,  metabolism,  pathology
Hydroxamic Acids / therapeutic use*
Oxalates / therapeutic use*
P-Glycoprotein / metabolism
Precancerous Conditions / chemically induced,  drug therapy*,  metabolism
Rats, Sprague-Dawley
Spleen / metabolism
Survival Rate
Tumor Cells, Cultured
Verapamil / pharmacology
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Benzeneacetamides; 0/Calcium Channel Blockers; 0/Carcinogens; 0/Hydroxamic Acids; 0/Oxalates; 0/P-Glycoprotein; 0/oxalyl bis(N-phenyl)hydroxamic acid; 23214-92-8/Doxorubicin; 52-53-9/Verapamil; 53-96-3/2-Acetylaminofluorene; 70-18-8/Glutathione

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