Abstract
The synthesis of three potent new antitumor agents is described: the A83586C-citropeptin hybrid (1), the A83586C-GE3 hybrid (2), and l-Pro-A83586C (3). Significantly, compounds 1 and 2 function as highly potent inhibitors of beta-catenin/TCF4 signaling within cancer cells, while simultaneously downregulating osteopontin (Opn) expression. A83586C antitumor cyclodepsipeptides also inhibit E2F-mediated transcription by downregulating E2F1 expression and inducing dephosphorylation of the oncogenic hyperphosphorylated retinoblastoma protein (pRb).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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DNA-Binding Proteins / antagonists & inhibitors*
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Depsipeptides / chemical synthesis*
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Depsipeptides / chemistry
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Depsipeptides / pharmacology*
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Drug Screening Assays, Antitumor
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E2F Transcription Factors / metabolism*
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E2F1 Transcription Factor / metabolism
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Humans
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Inhibitory Concentration 50
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Transcription Factor 4
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Transcription Factors / antagonists & inhibitors*
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beta Catenin / antagonists & inhibitors*
Substances
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Antineoplastic Agents
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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DNA-Binding Proteins
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Depsipeptides
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E2F Transcription Factors
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E2F1 Transcription Factor
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TCF4 protein, human
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Transcription Factor 4
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Transcription Factors
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beta Catenin
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A 83586C