Increased caspase-2 activity is associated with induction of apoptosis in IFN-beta sensitive melanoma cell lines.
Interferon (IFN) is believed to be one of the most effective anti-melanoma agents. Specifically, IFN-beta has the ability to induce apoptosis of melanoma cells. Induction of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has also been suggested to have a critical role in IFN-beta-induced apoptosis. To characterize the signaling pathway involved in IFN-beta-induced apoptosis, we analyzed the biological effects of IFN-beta on the cell death and caspase activation of melanoma cells. IFN-sensitive cell lines, MM418, SK-mel-23, and SK-mel-118, showed increased apoptotic populations correlated with the activation of caspase-2 and caspase-3 by IFN-beta. IFN-beta-induced apoptosis was significantly suppressed by inhibitors for caspase-2 or caspase-3, but not by inhibitors for caspase-8 or caspase-9 in these cell lines. TRAIL expression was observed in IFN-beta-treated cells of SK-mel-23 and SK-mel-118, but not in those cells of MM418, which showed massive IFN-beta-induced apoptosis and resistance to exogenous TRAIL-mediated apoptosis. G361 was resistant to IFN-beta-induced apoptosis but sensitive to exogenous TRAIL-mediated apoptosis. Furthermore, IFN-beta pretreatment significantly increased the sensitivity against exogenous TRAIL-mediated apoptosis and activation of caspase-2 in G361. These results suggested that caspase-2 activation is commonly associated with induction of IFN-beta-induced apoptosis in IFN-beta-sensitive melanoma cells.
Kamiya
Takafumi
T
Department of Dermatology, Sapporo Medical University School of Medicine , Sapporo, Hokkaido, Japan.
Okabayashi
Tamaki
T
Yokota
Shin-Ichi
S
Kan
Yuji
Y
Ogino
Jiro
J
Yamashita
Toshiharu
T
Fujii
Nobuhiro
N
Jimbow
Kowichi
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053143:Caspase 2 / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D008545:Melanoma / Q000188:drug therapy / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism
D000970:Antineoplastic Agents; D053221:TNF-Related Apoptosis-Inducing Ligand; D016899:Interferon-beta; D053143:Caspase 2; D053148:Caspase 3