Adenosine triphosphate-dependent transport of leukotriene c4 by membrane vesicles prepared from cisplatin-resistant human epidermoid carcinoma tumor cells

Ryuichi Fujii, Masato Mutoh, Tomoyuki Sumizawa, Zhe sheng Chen, Akihiko Yoshimura, Shin ichi Akiyama

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Abstract

Background: Cisplatin accumulation is decreased in many cisplatin-resistant cells. An active efflux pump for cisplatin exists in cisplatin-resistant human epidermoid carcinoma cells (called KB cells). A previous study has suggested that the adenosine triphosphate (ATP)-dependent glutathione S-con-jugate export pump (GS-X pump), which exports the bis-(glutathionato)-platinum (II) (GS-platinum) complex, could contribute to cellular resistance to cisplatin. Purpose: In this study, we examined whether the active efflux pump for cisplatin in the cisplatin-resistant KB cells is the GS-X pump and tested its activity by using an endogenous substrate, [3H]leukotriene C4 ([3H]LTC4). Methods: Membrane vesicles were prepared from KB-3-1 (clone from parental KB cells) cells and from cisplatin-resistant KCP-4 (a mutant clone derived from KB-3-1 cells) cells. Using a filtration technique, we measured the uptake and transport of [3H]LTC4, a substrate for the GS-X pump, into membrane vesicles at 37°C. Results: The uptake of [3H]LTC4 in the membrane vesicles from both the KB-3-1 and KCP-4 cells was ATP-de-pendent. In contrast, the ATP-de-pendent transport of [3H]LTC4 was observed only in KCP-4 membrane vesicles but not in KB-3-1 membrane vesicles. The ATP-dependent transport was vanadate sensitive and was inhibited by GS-platinum complex but only marginally by cisplatin and glutathione and not by vincristine or ver-apamil. The nucleotide triphosphates, guanosine triphosphate, cytidine triphosphate, uridine triphosphate, and deoxythymidine triphosphate could be substituted for ATP but were less efficient. A nonhydrolyzable ATP analogue, adenosine 5'-(β, γ-methylene) triphosphate, was not effective. Conclusions: The transport of LTC4 in membrane vesicles prepared from KCP-4 cells was facilitated by an ATP-dependent pump that appeared very similar to the GS-X pump. Implications: Our study suggests that the GS-X pump is involved in the decreased accumulation of cisplatin in KCP-4 cells. [J Natl Cancer Inst 86:1781-1784, 1994]

Original languageEnglish
Pages (from-to)1781-1784
Number of pages4
JournalJournal of the National Cancer Institute
Volume86
Issue number23
DOIs
Publication statusPublished - 1994 Jul 7
Externally publishedYes

Fingerprint

Cisplatin
Leukotriene C4
Adenosine
Vesicles
Tumors
Squamous Cell Carcinoma
Tumor
Membrane
Adenosine Triphosphate
Cells
Pumps
Membranes
Pump
Glutathione
Dependent
Cell
Neoplasms
KB Cells
Platinum
Clone

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Radiology Nuclear Medicine and imaging
  • Oncology
  • Cancer Research

Cite this

Adenosine triphosphate-dependent transport of leukotriene c4 by membrane vesicles prepared from cisplatin-resistant human epidermoid carcinoma tumor cells. / Fujii, Ryuichi; Mutoh, Masato; Sumizawa, Tomoyuki; Chen, Zhe sheng; Yoshimura, Akihiko; Akiyama, Shin ichi.

In: Journal of the National Cancer Institute, Vol. 86, No. 23, 07.07.1994, p. 1781-1784.

Research output: Contribution to journalArticle

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abstract = "Background: Cisplatin accumulation is decreased in many cisplatin-resistant cells. An active efflux pump for cisplatin exists in cisplatin-resistant human epidermoid carcinoma cells (called KB cells). A previous study has suggested that the adenosine triphosphate (ATP)-dependent glutathione S-con-jugate export pump (GS-X pump), which exports the bis-(glutathionato)-platinum (II) (GS-platinum) complex, could contribute to cellular resistance to cisplatin. Purpose: In this study, we examined whether the active efflux pump for cisplatin in the cisplatin-resistant KB cells is the GS-X pump and tested its activity by using an endogenous substrate, [3H]leukotriene C4 ([3H]LTC4). Methods: Membrane vesicles were prepared from KB-3-1 (clone from parental KB cells) cells and from cisplatin-resistant KCP-4 (a mutant clone derived from KB-3-1 cells) cells. Using a filtration technique, we measured the uptake and transport of [3H]LTC4, a substrate for the GS-X pump, into membrane vesicles at 37°C. Results: The uptake of [3H]LTC4 in the membrane vesicles from both the KB-3-1 and KCP-4 cells was ATP-de-pendent. In contrast, the ATP-de-pendent transport of [3H]LTC4 was observed only in KCP-4 membrane vesicles but not in KB-3-1 membrane vesicles. The ATP-dependent transport was vanadate sensitive and was inhibited by GS-platinum complex but only marginally by cisplatin and glutathione and not by vincristine or ver-apamil. The nucleotide triphosphates, guanosine triphosphate, cytidine triphosphate, uridine triphosphate, and deoxythymidine triphosphate could be substituted for ATP but were less efficient. A nonhydrolyzable ATP analogue, adenosine 5'-(β, γ-methylene) triphosphate, was not effective. Conclusions: The transport of LTC4 in membrane vesicles prepared from KCP-4 cells was facilitated by an ATP-dependent pump that appeared very similar to the GS-X pump. Implications: Our study suggests that the GS-X pump is involved in the decreased accumulation of cisplatin in KCP-4 cells. [J Natl Cancer Inst 86:1781-1784, 1994]",
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T1 - Adenosine triphosphate-dependent transport of leukotriene c4 by membrane vesicles prepared from cisplatin-resistant human epidermoid carcinoma tumor cells

AU - Fujii, Ryuichi

AU - Mutoh, Masato

AU - Sumizawa, Tomoyuki

AU - Chen, Zhe sheng

AU - Yoshimura, Akihiko

AU - Akiyama, Shin ichi

PY - 1994/7/7

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N2 - Background: Cisplatin accumulation is decreased in many cisplatin-resistant cells. An active efflux pump for cisplatin exists in cisplatin-resistant human epidermoid carcinoma cells (called KB cells). A previous study has suggested that the adenosine triphosphate (ATP)-dependent glutathione S-con-jugate export pump (GS-X pump), which exports the bis-(glutathionato)-platinum (II) (GS-platinum) complex, could contribute to cellular resistance to cisplatin. Purpose: In this study, we examined whether the active efflux pump for cisplatin in the cisplatin-resistant KB cells is the GS-X pump and tested its activity by using an endogenous substrate, [3H]leukotriene C4 ([3H]LTC4). Methods: Membrane vesicles were prepared from KB-3-1 (clone from parental KB cells) cells and from cisplatin-resistant KCP-4 (a mutant clone derived from KB-3-1 cells) cells. Using a filtration technique, we measured the uptake and transport of [3H]LTC4, a substrate for the GS-X pump, into membrane vesicles at 37°C. Results: The uptake of [3H]LTC4 in the membrane vesicles from both the KB-3-1 and KCP-4 cells was ATP-de-pendent. In contrast, the ATP-de-pendent transport of [3H]LTC4 was observed only in KCP-4 membrane vesicles but not in KB-3-1 membrane vesicles. The ATP-dependent transport was vanadate sensitive and was inhibited by GS-platinum complex but only marginally by cisplatin and glutathione and not by vincristine or ver-apamil. The nucleotide triphosphates, guanosine triphosphate, cytidine triphosphate, uridine triphosphate, and deoxythymidine triphosphate could be substituted for ATP but were less efficient. A nonhydrolyzable ATP analogue, adenosine 5'-(β, γ-methylene) triphosphate, was not effective. Conclusions: The transport of LTC4 in membrane vesicles prepared from KCP-4 cells was facilitated by an ATP-dependent pump that appeared very similar to the GS-X pump. Implications: Our study suggests that the GS-X pump is involved in the decreased accumulation of cisplatin in KCP-4 cells. [J Natl Cancer Inst 86:1781-1784, 1994]

AB - Background: Cisplatin accumulation is decreased in many cisplatin-resistant cells. An active efflux pump for cisplatin exists in cisplatin-resistant human epidermoid carcinoma cells (called KB cells). A previous study has suggested that the adenosine triphosphate (ATP)-dependent glutathione S-con-jugate export pump (GS-X pump), which exports the bis-(glutathionato)-platinum (II) (GS-platinum) complex, could contribute to cellular resistance to cisplatin. Purpose: In this study, we examined whether the active efflux pump for cisplatin in the cisplatin-resistant KB cells is the GS-X pump and tested its activity by using an endogenous substrate, [3H]leukotriene C4 ([3H]LTC4). Methods: Membrane vesicles were prepared from KB-3-1 (clone from parental KB cells) cells and from cisplatin-resistant KCP-4 (a mutant clone derived from KB-3-1 cells) cells. Using a filtration technique, we measured the uptake and transport of [3H]LTC4, a substrate for the GS-X pump, into membrane vesicles at 37°C. Results: The uptake of [3H]LTC4 in the membrane vesicles from both the KB-3-1 and KCP-4 cells was ATP-de-pendent. In contrast, the ATP-de-pendent transport of [3H]LTC4 was observed only in KCP-4 membrane vesicles but not in KB-3-1 membrane vesicles. The ATP-dependent transport was vanadate sensitive and was inhibited by GS-platinum complex but only marginally by cisplatin and glutathione and not by vincristine or ver-apamil. The nucleotide triphosphates, guanosine triphosphate, cytidine triphosphate, uridine triphosphate, and deoxythymidine triphosphate could be substituted for ATP but were less efficient. A nonhydrolyzable ATP analogue, adenosine 5'-(β, γ-methylene) triphosphate, was not effective. Conclusions: The transport of LTC4 in membrane vesicles prepared from KCP-4 cells was facilitated by an ATP-dependent pump that appeared very similar to the GS-X pump. Implications: Our study suggests that the GS-X pump is involved in the decreased accumulation of cisplatin in KCP-4 cells. [J Natl Cancer Inst 86:1781-1784, 1994]

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