Pleiotropic-resistant phenotype is a multifactorial phenomenon in human colon carcinoma cell lines

Toffoli, Giuseppe; Viel, Alessandra; Tumiotto, Loretta; Biscontin, Gabriella; Rossi, Claire; Boiocchi, Mauro

doi:10.1038/bjc.1991.11

Cited by 45 publications

(44 citation statements)

References 17 publications

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“…The DDP-resistant phenotype has been characterized in several human carcinomas, both in vitro and in vivo, and in some circumstances, it has been shown to include cross-resistance to gamma radiation, UV light, other heavy metals and platinum-containing drugs, methotrexate, and alkylating agents (for reviews see references 3-5). However, DDP resistance is not accompanied by resistance to drugs that participate in the multidrug-resistant phenotype mediated by the mdrl gene product (31,32); nor has it previously been reported to be accompanied by resistance to antimony-or arsenic-containing agents. In this study, four different human DDP-resistant tumor cell lines representing two different histologic types of cancer were found to be cross-resistant to antimony potassium tartrate.…”

Section: Discussionmentioning

confidence: 99%

Cross-resistance between cisplatin, antimony potassium tartrate, and arsenite in human tumor cells.

Naredi¹,

Heath²,

Enns³

et al. 1995

J. Clin. Invest.

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Cross-resistance between cisplatin (DDP) and metalloid salts in human cells was sought on the basis that mechanisms that mediate metalloid salt cross-resistance in prokaryotes are evolutionarily conserved. Two ovarian and two head and neck carcinoma cell lines selected for DDP resistance were found to be cross-resistant to antimony potassium tartrate, which contains trivalent antimony. The DDP-resistant variant 2008/A was also cross-resistant to arsenite but not to stibogluconate, which contains pentavalent antimony. A variant selected for resistance to antimony potassium tartrate was cross-resistant to DDP and arsenite. Resistance to antimony potassium tartrate and arsenite was of a similar magnitude (3-7-fold), whereas the level of resistance to DDP was greater (17-fold), irrespective of whether the cells were selected by exposure to DDP or to antimony potassium tartrate. In the resistant sublines, uptake of [3H] -dichloro(ethylenediamine) platinum(ll) was reduced to 41-52% of control, and a similar deficit was observed in the accumulation of arsenite. We conclude that DDP, antimony potassium tartrate, and arsenite all share a common mechanism of resistance in human cells and that this is due in part to an accumulation defect. (J. Clin. Invest. 1995.

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Section: Discussionmentioning

confidence: 99%

Cross-resistance between cisplatin, antimony potassium tartrate, and arsenite in human tumor cells.

Naredi¹,

Heath²,

Enns³

et al. 1995

J. Clin. Invest.

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“…They bind specifically to the 170 kD glycoprotein (P-glycoprotein) (Cornwell et al, 1987), which is responsible for this outward drug transport (Kartner et al, 1983); CDDP is not involved in MDR, as is shown by the fact that several MDR cell lines remained sensitive to CDDP (e.g. Toffoli et al, 1991) and that in CDDP resistant cell lines no elevated P-glycoprotein expression nor a DNA amplification of the MDR1 gene or an increased amount of mRNA could be detected (Kuppen et al, 1988;Masuda et al, 1988;Hospers et al, 1988a).…”

Section: Cddp Accumulation Restoring and Membrane Active Agentsmentioning

confidence: 99%

Modulation of cis-diamminedichloroplatinum(II) resistance: a review

Timmer‐Bosscha

Mulder²,

Vries³

1992

Br J Cancer

148

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Summary In this review an inventory is made of agents used to circumvent cis-diamminedichloroplatinum(II) (CDDP) resistance in vitro and in vivo. Agents that affect CDDP accumulation and membrane related systems, cytoplasmic defense mechanisms, as well as DNA accessibility and repair are reviewed.In resistant cell lines that have decreased accumulation, this can be restored by hyperthermic treatment. With or without effects on accumulation compounds that affect cell signal transduction often increase CDDP cytotoxicity. Calcium channel blockers and calmodulin inhibitors do not seem to be uniformly good modulators of CDDP resistance. For transduction modulators as well as cellular calcium affecting agents mechanisms are mainly unclear or controversial. Glutathione appears, with the now available agents, to be the most promising target for modulation of cytoplasmic defense mechanisms. At the nuclear level the inhibition of DNA repair related enzymes as well as the use of modified nucleosides to interfere with repair is studied in various cell lines. Results with these agents suggest opportunities for clinically feasible cytotoxicity modulation. DNA accessibility could in vitro be affected, but seems to be an unreliable target for modulation. Whenever possible the resistance mechanism affected and the mode of action of the modulator are discussed. As an alternative for modulation another method of overcoming CDDP resistance namely the application of CDDP analogues is considered.

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“…Drug efflux capacity sensitive to the L-type calcium channel and P-glycoprotein (multidrug resistance) inhibitor verapamil (20) was reported for these cell lines (21,22). PKI-587 growth inhibition in these cells was reevaluated in the presence of 10 mmol/L verapamil, which blocks P-glycoprotein function but does not affect cell growth or viability.…”

Section: Translational Relevancementioning

confidence: 99%