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CIRCUMVENTION OF ADRIAMYCIN RESISTANCE - EFFECT OF 2-METHYL-1,4-NAPHTHOQUINONE (VITAMIN-K3) ON DRUG CYTOTOXICITY IN SENSITIVE AND MDR-P388 LEUKEMIA-CELLS

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Title CIRCUMVENTION OF ADRIAMYCIN RESISTANCE - EFFECT OF 2-METHYL-1,4-NAPHTHOQUINONE (VITAMIN-K3) ON DRUG CYTOTOXICITY IN SENSITIVE AND MDR-P388 LEUKEMIA-CELLS
 
Creator PAREKH, HK
MANSURITORSHIZI, H
SRIVASTAVA, TS
CHITNIS, MP
 
Subject free-radical formation
breast tumor-cells
multidrug resistance
p388 leukemia
plasma-membrane
daunomycin
dna
metabolism
binding
invitro
multidrug resistance
circumvention
vitamin-k3
drug transport
dna binding
 
Description The effect of vitamin K3 (2-methyl-1,4-naphthoquinone) on Adriamycin (ADR) induced growth inhibition of drug sensitive and multidrug resistant P388 leukemia cells was evaluated. Exposure to ADR concentrations of 100-5000 ng simultaneously with 1-mu-M vitamin K3 elicited an enhanced inhibition of tumor cell survival. The effect of treatment with ADR alone, or in combination with vitamin K3 on DNA and RNA biosynthesis in the sensitive and resistant tumor cells, was also assessed. DNA and RNA biosynthesis inhibition was increased in P388/S (the parental cell line) and P388/ADR cells (the ADR resistant cell line which exhibits the multidrug resistant (MDR) phenotype) exposed to ADR after pretreatment for 3 h with vitamin K3. Concurrent administration in vivo of vitamin K3 and ADR illustrated a therapeutically significant increase (P < 0.05) in the life span of sensitive and resistant tumor cell bearing animals. Vitamin K3 caused a depletion of the intracellular glutathione (GSH) levels in P388/S and P388/ADR leukemia cells but at concentrations greater than those that enhanced ADR cytotoxicity. Pretreatment of the tumor cells with 1-mu-M vitamin K3 induced a 35 - 50 % (P < 0.001) elevation in the intracellular ADR accumulation in MDR P388 leukemia cells, while such an effect was absent in P388/S tumor cells. DNA binding studies performed utilizing calf thymus DNA, indicated that vitamin K3 enhanced the intercalation potential of ADR and also altered the equilibrium between the free and bound form of ADR in a cell free system. These factors and their possible effects on the potentiation of ADR cytotoxicity and the therapeutic significance of utilizing vitamin K3 as an adjuvant in the chemotherapy of MDR tumors is discussed.
 
Publisher ELSEVIER SCI IRELAND LTD
 
Date 2011-07-21T17:28:15Z
2011-12-26T12:52:06Z
2011-12-27T05:39:06Z
2011-07-21T17:28:15Z
2011-12-26T12:52:06Z
2011-12-27T05:39:06Z
1992
 
Type Article
 
Identifier CANCER LETTERS, 61(2), 147-156
0304-3835
http://dx.doi.org/10.1016/0304-3835(92)90173-S
http://dspace.library.iitb.ac.in/xmlui/handle/10054/5937
http://hdl.handle.net/10054/5937
 
Language en