BIOCHEMICAL MODULATION OF DOXORUBICIN USING AN ISOPRENOID DERIVATIVE, N-1379 - PLASMA TRANSMEMBRANE POTENTIAL AS A TARGET SITE
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- Published online on: December 1, 1995 https://doi.org/10.3892/ijo.7.6.1395
- Pages: 1395-1399
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Abstract
A new isoprenoid derivative, N-1379, was evaluated as a modulating agent of doxorubicin (DOX)-induced anticancer efficacy. The level of plasma transmembrane potential, measured using DiOC6(3), correlated with cellular sensitivity to DOX in K562 myelogenous leukemia, SH101 stomach, and PH101 pancreatic cancer cells. Non-toxic N-1379 increased the cellular transmembrane potential and DOX efficacy for three cell lines. The modulation of membrane function was accompanied by increases of DOX accumulation and S/G(2)M phase population in these cells. Overexpression of a 170 kD plasma membrane glycoprotein (GP-170) was not observed in any cells examined. We suggest therefore that interaction between electronegative transmembrane potential and positive charge of DOX may be linked to intracellular DOX accumulation. N-1379 may augment DOX efficacy through its increasing effect on plasma membrane potential independently of GP-170 overexpression.