title: Biochemical modulation of Doxorubicin using an isoprenoid derivative, N-1379 - plasma transmembrane potential as a target site.
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.
authors.forename: K
authors.initials: K
authors.lastname: Aogi
authors.forename: M
authors.initials: M
authors.lastname: Nishiyama
authors.forename: S
authors.initials: S
authors.lastname: Saeki
authors.forename: N
authors.initials: N
authors.lastname: Hirabayashi
authors.forename: T
authors.initials: T
authors.lastname: Toge