Modulation of doxorubicin sensitivity by a novel organic compound, oxalyl bis (N-phenyl) hydroxamic acid on acetyl aminofluorene-induced preneoplastic hepatocytes.
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.
Choudhuri
S K
SK
Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Calcutta 700026, India. soumitra01@vsnl.net
Majumder
Surajit
S
D015073:2-Acetylaminofluorene / Q000633:toxicity*; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D044482:Benzeneacetamides / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002273:Carcinogens / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D010070:Oxalates / Q000627:therapeutic use*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000378:metabolism; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D044482:Benzeneacetamides; D002121:Calcium Channel Blockers; D002273:Carcinogens; D006877:Hydroxamic Acids; D010070:Oxalates; C117053:oxalyl bis(N-phenyl)hydroxamic acid; D004317:Doxorubicin; D015073:2-Acetylaminofluorene; D014700:Verapamil; D005978:Glutathione