Benzquinamide inhibits P-glycoprotein mediated drug efflux and potentiates anticancer agent cytotoxicity in multidrug resistant cells

Roberto Mazzanti, James Croop, Zenaida Gatmaitan, Mark Budding, Kim Steiglitz, Robert Arceci, Irwin M. Arias

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

We have previously shown that efflux of cytotoxic drugs from multidrug resistant (MDR) cell lines can be quantitated at the single cell level using a sensitive fluorescence microscopy technique. Based on the structure of compounds which inhibited the efflux of Rhodamine-123 (Rho-123) using this methodology, we hypothesized that the antiemetic, antihistaminic agent benzquinamide (BZQ) would interfere with P-glycoprotein (P-gp) mediated drug transport and potentiate the effects of anticancer agents in MDR cell lines. We show that BZQ interferes with P-gp mediated drug efflux and increases drug accumulation in MDR cells using Rho-123 as a fluorescent probe. BZQ increases the cytotoxicity of chemotherapeutic agents to both human and hamster MDR cell lines in vitro. A slight increase in cytotoxicity to chemotherapeutic agents is also observed in the parental cell lines with BZQ. BZQ increases [3H]daunorubicin accumulation and inhibits the binding of [125I]iodoaryl azidoprazosin to the P-gp in MDR cells. BZQ is a new agent to increase the cytotoxic effects of anticancer agents in MDR cells and may ultimately prove useful as an adjunct in cancer chemotherapy.

Original languageEnglish (US)
Pages (from-to)359-365
Number of pages7
JournalOncology Research
Volume4
Issue number8-9
StatePublished - 1992
Externally publishedYes

Fingerprint

P-Glycoprotein
Antineoplastic Agents
Pharmaceutical Preparations
Rhodamine 123
Cell Line
Daunorubicin
Antiemetics
Fluorescent Dyes
Fluorescence Microscopy
Cricetinae
benzquinamide
Drug Therapy
Neoplasms

ASJC Scopus subject areas

  • Cancer Research

Cite this

Mazzanti, R., Croop, J., Gatmaitan, Z., Budding, M., Steiglitz, K., Arceci, R., & Arias, I. M. (1992). Benzquinamide inhibits P-glycoprotein mediated drug efflux and potentiates anticancer agent cytotoxicity in multidrug resistant cells. Oncology Research, 4(8-9), 359-365.

Benzquinamide inhibits P-glycoprotein mediated drug efflux and potentiates anticancer agent cytotoxicity in multidrug resistant cells. / Mazzanti, Roberto; Croop, James; Gatmaitan, Zenaida; Budding, Mark; Steiglitz, Kim; Arceci, Robert; Arias, Irwin M.

In: Oncology Research, Vol. 4, No. 8-9, 1992, p. 359-365.

Research output: Contribution to journalArticle

Mazzanti, R, Croop, J, Gatmaitan, Z, Budding, M, Steiglitz, K, Arceci, R & Arias, IM 1992, 'Benzquinamide inhibits P-glycoprotein mediated drug efflux and potentiates anticancer agent cytotoxicity in multidrug resistant cells', Oncology Research, vol. 4, no. 8-9, pp. 359-365.
Mazzanti, Roberto ; Croop, James ; Gatmaitan, Zenaida ; Budding, Mark ; Steiglitz, Kim ; Arceci, Robert ; Arias, Irwin M. / Benzquinamide inhibits P-glycoprotein mediated drug efflux and potentiates anticancer agent cytotoxicity in multidrug resistant cells. In: Oncology Research. 1992 ; Vol. 4, No. 8-9. pp. 359-365.
@article{de03ec4cf70a4537bc838e8e9581aa4c,
title = "Benzquinamide inhibits P-glycoprotein mediated drug efflux and potentiates anticancer agent cytotoxicity in multidrug resistant cells",
abstract = "We have previously shown that efflux of cytotoxic drugs from multidrug resistant (MDR) cell lines can be quantitated at the single cell level using a sensitive fluorescence microscopy technique. Based on the structure of compounds which inhibited the efflux of Rhodamine-123 (Rho-123) using this methodology, we hypothesized that the antiemetic, antihistaminic agent benzquinamide (BZQ) would interfere with P-glycoprotein (P-gp) mediated drug transport and potentiate the effects of anticancer agents in MDR cell lines. We show that BZQ interferes with P-gp mediated drug efflux and increases drug accumulation in MDR cells using Rho-123 as a fluorescent probe. BZQ increases the cytotoxicity of chemotherapeutic agents to both human and hamster MDR cell lines in vitro. A slight increase in cytotoxicity to chemotherapeutic agents is also observed in the parental cell lines with BZQ. BZQ increases [3H]daunorubicin accumulation and inhibits the binding of [125I]iodoaryl azidoprazosin to the P-gp in MDR cells. BZQ is a new agent to increase the cytotoxic effects of anticancer agents in MDR cells and may ultimately prove useful as an adjunct in cancer chemotherapy.",
author = "Roberto Mazzanti and James Croop and Zenaida Gatmaitan and Mark Budding and Kim Steiglitz and Robert Arceci and Arias, {Irwin M.}",
year = "1992",
language = "English (US)",
volume = "4",
pages = "359--365",
journal = "Oncology Research",
issn = "0965-0407",
publisher = "Cognizant Communication Corporation",
number = "8-9",

}

TY - JOUR

T1 - Benzquinamide inhibits P-glycoprotein mediated drug efflux and potentiates anticancer agent cytotoxicity in multidrug resistant cells

AU - Mazzanti, Roberto

AU - Croop, James

AU - Gatmaitan, Zenaida

AU - Budding, Mark

AU - Steiglitz, Kim

AU - Arceci, Robert

AU - Arias, Irwin M.

PY - 1992

Y1 - 1992

N2 - We have previously shown that efflux of cytotoxic drugs from multidrug resistant (MDR) cell lines can be quantitated at the single cell level using a sensitive fluorescence microscopy technique. Based on the structure of compounds which inhibited the efflux of Rhodamine-123 (Rho-123) using this methodology, we hypothesized that the antiemetic, antihistaminic agent benzquinamide (BZQ) would interfere with P-glycoprotein (P-gp) mediated drug transport and potentiate the effects of anticancer agents in MDR cell lines. We show that BZQ interferes with P-gp mediated drug efflux and increases drug accumulation in MDR cells using Rho-123 as a fluorescent probe. BZQ increases the cytotoxicity of chemotherapeutic agents to both human and hamster MDR cell lines in vitro. A slight increase in cytotoxicity to chemotherapeutic agents is also observed in the parental cell lines with BZQ. BZQ increases [3H]daunorubicin accumulation and inhibits the binding of [125I]iodoaryl azidoprazosin to the P-gp in MDR cells. BZQ is a new agent to increase the cytotoxic effects of anticancer agents in MDR cells and may ultimately prove useful as an adjunct in cancer chemotherapy.

AB - We have previously shown that efflux of cytotoxic drugs from multidrug resistant (MDR) cell lines can be quantitated at the single cell level using a sensitive fluorescence microscopy technique. Based on the structure of compounds which inhibited the efflux of Rhodamine-123 (Rho-123) using this methodology, we hypothesized that the antiemetic, antihistaminic agent benzquinamide (BZQ) would interfere with P-glycoprotein (P-gp) mediated drug transport and potentiate the effects of anticancer agents in MDR cell lines. We show that BZQ interferes with P-gp mediated drug efflux and increases drug accumulation in MDR cells using Rho-123 as a fluorescent probe. BZQ increases the cytotoxicity of chemotherapeutic agents to both human and hamster MDR cell lines in vitro. A slight increase in cytotoxicity to chemotherapeutic agents is also observed in the parental cell lines with BZQ. BZQ increases [3H]daunorubicin accumulation and inhibits the binding of [125I]iodoaryl azidoprazosin to the P-gp in MDR cells. BZQ is a new agent to increase the cytotoxic effects of anticancer agents in MDR cells and may ultimately prove useful as an adjunct in cancer chemotherapy.

UR - http://www.scopus.com/inward/record.url?scp=0026988983&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026988983&partnerID=8YFLogxK

M3 - Article

VL - 4

SP - 359

EP - 365

JO - Oncology Research

JF - Oncology Research

SN - 0965-0407

IS - 8-9

ER -