[Merocyanine 540-mediated photodynamic therapy inhibits P-glycoprotein (P-gp) activity in adriamycin-resistant K562 cells].
The photosensitizing dye merocyanine 540 (MC540) has been used in preclinical models and in a phase I clinical trial in the U.S.A. for the extracorporeal purging of autologous bone marrow grafts contaminated with leukemia or lymphoma. In this communication, we report MC540-mediated photodynamic therapy (PDT) was effective in purging leukemic cells expressing P-gp. When K562 and K562/ADM were exposed to MC540 (15 micrograms/ml) and white light (145.8 kJ/m2), the concentration of K562 and K 562/ADR was reduced by 1.8 and 3.0 log, respectively. Using flow cytometry and confocal laser scan microscopy, MC540 and calcein-AM were bound intracellularly and effluxed by P-gp in K562/ADM. In K562/ADM, calcein-AM efflux was inhibited by P-gp modulator, cyclosporin A (5 microM) and verapamil (15 micrograms/ml). In contrast, MC540 efflux was inhibited by cyclosporin A but not verapamil. Furthermore, MC540-mediated PDT inhibited efflux of calcein-AM and MC540, and induced the accumulation of dyes in K562/ADM. We conclude that MC540 is a substrate of P-gp and that MC540-mediated PDT is useful for purging MDR cells through inhibition of P-gp activity.
Sato
Y
Y
First Dept. of Internal Medicine, Nihon University School of Medicine.
Yamazaki
T
T
Yasukawa
K
K
Kaneita
Y
Y
Mochimaru
J
J
Hanai
M
M
Irie
T
T
Kura
Y
Y
Sawada
U
U
Horie
T
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011744:Pyrimidinones / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D011744:Pyrimidinones; C003954:merocyanine dye; D004317:Doxorubicin