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Enhancement of Photodynamic Cell Killing (with Chloroaluminum Phthalocyanine) by Treatment of V79 Cells with the Ionophore Nigericin¹

Divisions of Biochemical Oncology and Radiation Oncology, Department of Radiology, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio 44106

The K⁺/H⁺ ionophore nigericin dramatically increases killing of V79 cells by photodynamic therapy (PDT), when cells pretreated with 1 µM chloroaluminum phthalocyanine are incubated with nigericin before exposure to red light. Nigericin affects primarily the shoulder of the PDT dose-response curve, reducing the surviving fraction from 0.90 to 0.02 after a fluence of 7 kJ/m² and from 0.80 to 0.0003 after a fluence of 12 kJ/m². Optimal enhancement of PDT occurs when cells are incubated with 2 µM nigericin, at pH_e, 6.7, for 30 to 60 min before irradiation. However, significant enhancement of PDT also occurs when nigericin is added immediately before irradiation. Treatments with chloroaluminum phthalocyanine and nigericin, nigericin alone, or nigericin and red light are not toxic to cells. Cells treated with the combined agents display a rounded morphology 2 h after light exposure and lyse within 12 h. However, rounding of cells is not accompanied by severe depletion of ATP or by permeabilization of the plasma membrane to trypan blue. These results, together with known metabolic effects of nigericin, suggest that nigericin potentiates PDT by perturbing ion transport across either mitochondrial or plasma membranes.

¹ This research was supported by Research Grant RO1 CA 40516 and by Cancer Center Support Grant P30 CA 43703 from the National Cancer Institute, Department of Health and Human Services, and by a generous gift from the Marguerite M. Wilson Foundation.

² To whom requests for reprints should be addressed, at Division of Biochemical Oncology, Department of Radiology, University Hospitals of Cleveland, 2058 Abington Road, Wearn B-21, Cleveland, OH 44106.

Received 8/ 7/89. Revised 11/13/89. Accepted 11/15/89.