Effects of the multidrug transporter P-glycoprotein on cellular responses to ionizing radiation

• Published in: Cancer research (Chicago, Ill.) Vol. 60; no. 10; pp. 2576 - 2578
• Main Authors: RUTH, A. C, RONINSON, I. B
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-05-2000
• Subjects: 3T3 Cells; Ageing, cell death; Animals; Apoptosis - drug effects; Apoptosis - radiation effects; ATP-Binding Cassette, Sub-Family B, Member 1 - pharmacology; Biological and medical sciences; Cell physiology; Cell Survival - drug effects; Cell Survival - radiation effects; Cellular Senescence - drug effects; Cellular Senescence - radiation effects; Fundamental and applied biological sciences. Psychology; HeLa Cells; Humans; Mice; Mitosis - drug effects; Mitosis - radiation effects; Molecular and cellular biology; Radiation, Ionizing; Antineoplastic agent; Human; Cell proliferation; Drug; Senescence; Cytostatic; Mitosis; Gene product; P Glycoprotein; In vitro; Conveyor; Biological activity; Gamma irradiation; Ionizing irradiation; Transfection; Gene; Cell death; Multiple resistance; Established cell line; Inhibition; Apoptosis
• ISSN: 0008-5472; 1538-7445

Ionizing radiation induces apoptosis, mitotic catastrophe, and senescence-like terminal proliferation arrest in tumor cells. We investigated the effect of the MDR1 P-glycoprotein (Pgp), recently shown to inhibit caspase-mediated apoptosis, on cellular responses to radiation. Pgp strongly inhibited radiation-induced apoptosis in a HeLa-derived cell line with inducible MDR1 expression and in NIH 3T3 cells transduced with a MDR1-expressing retroviral vector. The inhibition of apoptosis by Pgp was associated, however, with increases in radiation-induced mitotic catastrophe and senescence and produced only a marginal change in the survival of irradiated cells. Pgp had no effect on radiation responses in apoptosis-resistant HT1080 cells. These results indicate that Pgp inhibits radiation-induced apoptosis, but this effect of Pgp provides no substantial increase in radiation resistance of the tested cell lines because apoptosis-resistant cells die from mitotic catastrophe or undergo senescence-like terminal proliferation arrest.