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KINK-1, a novel small-molecule inhibitor of IKKbeta, enhances susceptibility of melanoma cells to antitumoral treatment

ABSTRACT: Interference with chemoresistance to enhance the efficacy of chemotherapeutics may be of great utility for cancer therapy. We have identified KINK-1 (Kinase Inhibitor of NF-kappaB-1), a highly selective small-molecule IKKkappa inhibitor, as a potent suppressor of both constitutive and induced NF-kappaB activity in melanoma cells. While KINK-1 profoundly diminished various NF-kappaB-dependent gene products regulating proliferation, cytokine production or anti-apoptotic responses, the compound by itself showed little antiproliferative or pro-apoptotic activity on the cellular level. However, its combination with some cytostatics markedly enhanced their antitumoral activities in vitro, and doxorubicin-induced NF-kappaB activation, a mechanism implicated in chemoresistance, was abrogated by KINK-1. In addition, when KINK-1 was combined with doxorubicin in an in vivo melanoma model, experimental metastasis was significantly diminished as compared to either treatment alone. Induction of chemoresistance by KINK-1 in vivo was not observed. Thus, KINK-1 or related substances might increase the susceptibility of tumors to chemotherapy. Keywords: time-course

ORGANISM(S): Homo sapiens

PROVIDER: GSE8772 | GEO | 2008/08/09

SECONDARY ACCESSION(S): PRJNA102059

REPOSITORIES: GEO

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Transcription profiling of human melanoma cells reveals KINK-1 a novel small-molecule inhibitor of IKK, enhances susceptibility of melanoma cells to antitumoral treatment

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