Increased caspase-2 activity is associated with induction of apoptosis in IFN-beta sensitive melanoma cell lines.

Abstract

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.

• Authors: Takafumi Kamiya, Tamaki Okabayashi, Shin-Ichi Yokota, Yuji Kan, Jiro Ogino, Toshiharu Yamashita, Nobuhiro Fujii, Kowichi Jimbow
• Journal: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 30 Issue 5 Pg. 349-57 (May 2010) ISSN: 1557-7465 [Electronic] United States
• PMID: 20187765 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• TNF-Related Apoptosis-Inducing Ligand
• Interferon-beta
• Caspase 2
• Caspase 3

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Caspase 2 (genetics, metabolism)
• Caspase 3 (genetics, metabolism)
• Cell Line, Tumor
• Drug Resistance, Neoplasm (drug effects)
• Enzyme Activation (drug effects)
• Humans
• Interferon-beta (pharmacology)
• Melanoma (drug therapy, enzymology, immunology, pathology)
• Signal Transduction (drug effects)
• TNF-Related Apoptosis-Inducing Ligand (metabolism)