title: AV-65, a novel Wnt/β-catenin signal inhibitor, successfully suppresses progression of multiple myeloma in a mouse model.
abstract: Multiple myeloma (MM) is a malignant neoplasm of plasma cells. Although new molecular targeting agents against MM have been developed based on the better understanding of the underlying pathogenesis, MM still remains an incurable disease. We previously demonstrated that β-catenin, a downstream effector in the Wnt pathway, is a potential target in MM using RNA interference in an in vivo experimental mouse model. In this study, we have screened a library of more than 100 000 small-molecule chemical compounds for novel Wnt/β-catenin signaling inhibitors using a high-throughput transcriptional screening technology. We identified AV-65, which diminished β-catenin protein levels and T-cell factor transcriptional activity. AV-65 then decreased c-myc, cyclin D1 and survivin expression, resulting in the inhibition of MM cell proliferation through the apoptotic pathway. AV-65 treatment prolonged the survival of MM-bearing mice. These findings indicate that this compound represents a novel and attractive therapeutic agent against MM. This study also illustrates the potential of high-throughput transcriptional screening to identify candidates for anticancer drug discovery.
authors: H
authors: H
authors: Yao
authors: E
authors: E
authors: Ashihara
authors: J W
authors: JW
authors: Strovel
authors: Y
authors: Y
authors: Nakagawa
authors: J
authors: J
authors: Kuroda
authors: R
authors: R
authors: Nagao
authors: R
authors: R
authors: Tanaka
authors: A
authors: A
authors: Yokota
authors: M
authors: M
authors: Takeuchi
authors: Y
authors: Y
authors: Hayashi
authors: C
authors: C
authors: Shimazaki
authors: M
authors: M
authors: Taniwaki
authors: K
authors: K
authors: Strand
authors: J
authors: J
authors: Padia
authors: H
authors: H
authors: Hirai
authors: S
authors: S
authors: Kimura
authors: T
authors: T
authors: Maekawa