Apoptotic effect of ganciclovir on primary effusion lymphoma cells infected with Kaposi's sarcoma-associated herpesvirus.
We evaluated the cytotoxic and apoptotic effects of two purine nucleoside analogues, acyclovir (ACV) and ganciclovir (GCV), on lymphoma cells stably harboring Kaposi's sarcoma-associated herpesvirus (KSHV). Colorimetric caspase assay, flow cytometry, and immunoblotting with antibodies against apoptosis-related molecules revealed that GCV has cytotoxic activity toward KSHV-infected primary effusion lymphoma cells, while ACV has weak or little activity. In addition to the GCV-induced cytotoxicity, apoptosis via caspase-7/8, cleavage of poly(ADP-ribose) polymerase, and accumulation of p53 and p21 were induced by GCV treatment. In contrast, neither ACV nor GCV have cytotoxicity- or apoptosis-inducing activities toward uninfected cells.
Fujimuro
Masahiro
M
Department of Biochemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan fuji2@pharm.hokudai.ac.jp
Inoue
Hisanori
H
Teishikata
Yasuhiro
Y
Ishida
Yuriko
Y
Yokosawa
Hideyoshi
H
D000212:Acyclovir / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D015774:Ganciclovir / Q000494:pharmacology* / Q000627:therapeutic use; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000473:pathology / Q000821:virology*; D014407:Tumor Cells, Cultured
D053148:Caspase 3; D053179:Caspase 7; D015774:Ganciclovir; D000212:Acyclovir