Resistance of human multidrug-resistant neoplastic cell lines to paclitaxel-induced-radiosensitization is reduced by the non-immunosuppressive cyclosporine analog SDZ PSC 833

J Sedlak; L Hunakova; M Chorvath; M Sulikova; L Novotny; E Boljesikova; R Zeillinger; B Chorvath

Resistance of human multidrug-resistant neoplastic cell lines to paclitaxel-induced-radiosensitization is reduced by the non-immunosuppressive cyclosporine analog SDZ PSC 833

Anticancer Res. 1998 Jul-Aug;18(4C):3099-105.

Authors

J Sedlak¹, L Hunakova, M Chorvath, M Sulikova, L Novotny, E Boljesikova, R Zeillinger, B Chorvath

Affiliation

¹ Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovakia.

PMID: 9713517

Abstract

The non-immunosuppressive cyclosporine analog SDZ PSC 833 abolished the resistance of human multidrug resistant (MDR-1, P-gp) human promyelocyte leukemia HL-60/VCR cells in vitro to paclitaxel-induced cell cycle- and viability alterations, as well as resistance to paclitaxel-induced radiosensitization. Furthermore, SDZ PSC 833 abolished also the resistance of human multidrug-resistant ovarian A2780/ADR cells to paclitaxel-induced cell cycle alterations and reduced its resistance to paclitaxel-induced radiosensitization. In these multidrug-resistant ovarian carcinoma cells the supra-additive interaction between paclitaxel and SDZ PSC 833 pre-exposure and subsequent irradiation appeared at slightly higher paclitaxel concentrations (40-100 nM) compared to those required for a similar interaction in the parental drug sensitive A2780 cells (40-80 nM paclitaxel).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B, Member 1 / drug effects
ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology
Antineoplastic Agents, Phytogenic / administration & dosage
Antineoplastic Agents, Phytogenic / antagonists & inhibitors
Antineoplastic Agents, Phytogenic / pharmacology*
Antineoplastic Combined Chemotherapy Protocols / pharmacology
Apoptosis / drug effects
Apoptosis / physiology
Cell Cycle / drug effects
Cell Survival / drug effects
Combined Modality Therapy
Cyclosporins / administration & dosage
Cyclosporins / pharmacology*
DNA, Neoplasm / drug effects
Drug Interactions
Drug Resistance, Multiple*
Female
HL-60 Cells / drug effects*
HL-60 Cells / radiation effects*
Humans
Ovarian Neoplasms / drug therapy*
Ovarian Neoplasms / radiotherapy*
Paclitaxel / administration & dosage
Paclitaxel / antagonists & inhibitors
Paclitaxel / pharmacology*
Phospholipids / metabolism
Radiation Tolerance / drug effects*
Radiation-Sensitizing Agents / pharmacology*
Tumor Cells, Cultured

Substances

ATP Binding Cassette Transporter, Subfamily B, Member 1
Antineoplastic Agents, Phytogenic
Cyclosporins
DNA, Neoplasm
Phospholipids
Radiation-Sensitizing Agents
Paclitaxel
valspodar