Tanespimycin and tipifarnib exhibit synergism in inducing apoptosis in melanoma cell lines from later stages of tumor progression.
Many anticancer strategies rely on efficient induction of apoptosis. The need for development of drug combinations with a strong pro-apoptotic activity is of particular interest in melanoma resistant to currently available chemotherapeutic regimes. We studied the pro-apoptotic properties of combination of tanespimycin+tipifarnib in five melanoma cell lines representing various stages of tumor progression. Our results show that in cells derived from vertical- and metastatic-phase the combination of tested drugs is strongly cytotoxic and efficient in inducing apoptosis, as evidenced by activation of caspase-9 and caspase-3 and enhanced fragmentation of DNA.
Chair of Medical Biochemistry, Jagiellonian University Medical College , ul. Kopernika 7, Kraków , Poland.
Anna
A
Bentke
Jędrzej
J
Małecki
Barbara
B
Ostrowska
Katarzyna
K
Krzykowska-Petitjean
Piotr
P
Laidler
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D015363:Quinolones / Q000494:pharmacology*
D000970:Antineoplastic Agents; D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D015363:Quinolones; C112765:tanespimycin; D017346:Protein Serine-Threonine Kinases; D053148:Caspase 3; D053453:Caspase 9; C402769:tipifarnib