Sensitization of multidrug-resistant human leukemia cells with MDR1-targeted antisense and inhibition of drug-mediated MDR1 induction

Li, X; Smyth, A.; Barrett, DJ; Ivy, S. Percy; Hofe, Eric von

doi:10.1038/sj.leu.2400696

Cited by 18 publications

(14 citation statements)

References 3 publications

(6 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These cell lines represent a minor fraction of the developmental stages described for T-cell ontogeny (Bene et al, 1995;Burger et al, 1999;Wuchter et al, 2002). While most of these drug resistance studies have used only the CCRF-CEM or MOLT-4 cell lines (McGrath et al, 1989;Li et al, 1997), CCRF-CEM cells represent a Pre-T (CD1a ) surface CD3 ) ) stage of differentiation (Burger et al, 1999), and MOLT-4 shows immunophenotypic and genotypic features of natural kill (NK) cells. Furtheremore, while the direct investigation of patient samples remains an important goal in translational research, such studies are often difficult to conduct ex vivo (Manabe et al, 1992).…”

mentioning

confidence: 99%

Genetic alterations determine chemotherapy resistance in childhood T‐ALL: modelling in stage‐specific cell lines and correlation with diagnostic patient samples

Estes¹,

Lovato²,

Khawaja³

et al. 2007

Br J Haematol

View full text Add to dashboard Cite

Summary Acquired drug resistance eventually leads to treatment failure in T‐cell acute lymphoblastic leukaemia (T‐ALL). Immunophenotypic and cytogenetic heterogeneities within T‐ALL influence susceptibility to cytotoxic therapy, and little is known about the mechanisms of drug resistance at specific stages of T‐cell ontogeny. We developed tolerance to therapeutic concentrations of daunorubicin (DNR) and l‐asparaginase (l‐asp) in Jurkat (CD1a−, sCD3+) and Sup T1 (CD1a+, sCD3−) cell lines, having respective ‘mature’ and ‘cortical’ stages of developmental arrest. DNR resistant cells acquired multidrug resistance: 310‐fold increased resistance to vincristine (VCR) and a 120‐fold increased resistance to prednisolone (PRED). Microarray analysis identified upregulation of asparagine synthetase (ASNS) and argininosuccinate synthase 1 (ASS1) to cell lines with acquired resistance to l‐asp, and in the case of DNR, upregulation of ATP‐binding cassette B1 (ABCB1). Suppression of ABCB1, ASNS and ASS1 by RNA interference revealed their functional relevance to acquired drug resistance. Expression profiling of these genes in 80 T‐ALL patients showed correlation with treatment response. This study expands the pool of available drug resistant cell lines having cortical and mature stages of developmental arrest, introduces three new drug resistant T‐ALL cell lines, and identifies gene interactions leading to l‐asp and DNR resistance.

show abstract

mentioning

confidence: 99%

Genetic alterations determine chemotherapy resistance in childhood T‐ALL: modelling in stage‐specific cell lines and correlation with diagnostic patient samples

Estes¹,

Lovato²,

Khawaja³

et al. 2007

Br J Haematol

View full text Add to dashboard Cite

show abstract

“…The mechanism for which the majority of oligonucleotides have been designed to date is to cause translational arrest by binding to the translation initiation codon or alternatively to bind to areas in the coding region to attempt steric hindrance of ribosome progression along the mRNA (Brysch and Schilingensiepen, 1994;Crooke and Bennett, 1996;Ohkawa et al, 1996;Bouffard et al, 1996;Probst and Skutella, 1996). Although the ribosomal machinery is quite powerful and tends to sweep away most obstacles in its path, targeting the AUG initiation codon where the ribosomes first begin translational has been shown to be a very effective target (Vasanthakumar and Ahmed, 1989;Jaroszewski et al, 1990;Rivoltini et al, 1990;Clynes et al, 1992;Corrias et al, 1992;Efferth et al, 1993;Thierry et al, 1993;Quattrone et al, 1994b;Nakashima et al, 1995;Alahari et al, 1996;Cucco and Calabretta, 1996;Sola and Colombani, 1996;Hirtake et al, 1997;Li et al, 1997).…”

Section: Antisense Technologymentioning

confidence: 99%

“…Li and his co-workers designed three antisense phosphorothioate oligonucleotides to mdr-1 (Li et al, 1997). One (1729) was just inside the coding region from bases +12 to +36, another (474) was targeted to the last 20 bases of the 5 untranslated region (-20 to -1), while the last oligo (1795) had the same sequence as 474 but with four 2 -O-methyl modified sugar linked bases at both ends (Table I).…”

Section: Use Of Antisense Oligonucleotides To Inhibit Mdr-1 Expressionmentioning

confidence: 99%

Untitled

et al. 1998

View full text Add to dashboard Cite

Chemotherapy can cure a number of human cancers but resistance (either intrinsic or acquired) remains a significant problem in many patients and in many types of solid tumour. Combination chemotherapy (using drugs with different cellular targets/mechanisms) was introduced in order to kill cells which had developed resistance to a specific drug, and to allow delivery of a greater total dose of anti-cancer chemicals by combining drugs with different side-effects (Pratt et al., 1994). Nearly all anti-cancer drugs kill tumour cells by activating an endogenous bio-chemical pathway for cell suicide, known as programmed cell death or apoptosis.

show abstract

“…A number of antisense oligodeoxynucleotides (ODNs) and vectors are reported to enhance the cytotoxicity of various drugs, by targeting modulators of drug activity and cell response as opposed to the drug target per se , with mdr1 and bcl‐2 being the most common targets of antisense (Cucco & Calabretta, 1996; Kitada et al ., 1994; Li et al ., 1997; Luo et al ., 1999; Miayake et al ., 2000; Quattrone et al ., 1994; Thierry et al ., 1993). Based on the success of in vivo screening of antisense ODNs, at least seven of these agents are currently in clinical trial for anti‐cancer treatment, with targets including bcl‐2 (Chen et al ., 2000; Scher et al ., 2000; Waters et al ., 2000) and p53 (Bishop et al ., 1996).…”

Section: Introductionmentioning

confidence: 99%

Antisense‐induced down‐regulation of thymidylate synthase and enhanced cytotoxicity of 5‐FUdR in 5‐FUdR‐resistant HeLa cells

Ferguson

DeMoor

Vincent

et al. 2001

British J Pharmacology

View full text Add to dashboard Cite

1 Thymidylate synthase (TS) is a target for several anticancer drugs. We previously showed that an antisense oligodeoxynucleotide (ODN) directed against TS mRNA down-regulated TS protein and enhanced cytotoxicity of TS-targeting drugs [including 5-¯uorodeoxyuridine (5-FUdR)] in HeLa cells. Patient tumours with increased TS expression are resistant to TS-targeting drugs. It was hypothesized that TS mRNA and consequently TS protein could be down-regulated in 5-FUdRresistant cells that overexpress TS, sensitizing them to 5-FUdR cytotoxicity. In this study we assessed the capacity of an anti-TS antisense ODN to circumvent resistance dependent on TS overexpression. 2 Variant HeLa clones exhibiting 2 ± 20 fold resistance to 5-FUdR were selected by exposing cultured cells to drug. Clones FUdR-5a, -25b, and -50a expressed TS protein levels 10 fold, 10 fold, and 17 fold higher (respectively) than parental cells. Cells were treated with antisense ODN 83 (a 2'-methoxy-ethoxylated, phosphorothioated 20-mer, complementary to a portion of the 3'-untranslated region of TS mRNA), or ODN 32 (a control ODN with the same base composition as ODN 83, but in randomized order). Twenty-four and 48 h following transfection (50 ± 100 nMPCR) and protein levels (by radiolabelled 5-FUdR-monophosphate binding) were decreased by at least 60% in ODN 83-treated cells compared with control ODN 32-treated cells. ODN 83 enhanced the cytotoxicity of 5-FUdR by up to 85% in both parental and 5-FUdR-resistant cell lines. 3 Antisense ODN can be used to down-regulate TS and attenuate drug resistance in TSoverexpressing cells.

show abstract

Sensitization of multidrug-resistant human leukemia cells with MDR1-targeted antisense and inhibition of drug-mediated MDR1 induction

Abstract: expression. 15,18 This raises the possibility that failure of a com-

Cited by 18 publications

References 3 publications

Genetic alterations determine chemotherapy resistance in childhood T‐ALL: modelling in stage‐specific cell lines and correlation with diagnostic patient samples

Genetic alterations determine chemotherapy resistance in childhood T‐ALL: modelling in stage‐specific cell lines and correlation with diagnostic patient samples

Untitled

Antisense‐induced down‐regulation of thymidylate synthase and enhanced cytotoxicity of 5‐FUdR in 5‐FUdR‐resistant HeLa cells

Contact Info

Product

Resources

About