Abstract
Six new synthetic bile acid derivatives were synthesized and tested in vitro against various human cancer cells (glioblastoma multiforme (GBM), multiple myeloma (KMS-11), and colonic carcinoma (HCT-116) cell lines. The best activity was obtained with compound IIIb on multiple myeloma cells (LD(50): 8.5+/-0.5 microM). This activity was associated with Mcl-1 and PARP-1 cleavage, inhibition of NFkappaB signaling, and DNA fragmentation, demonstrating an apoptotic cell death signaling pathway.
MeSH terms
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Amides / chemical synthesis
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Amides / pharmacology*
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Apoptosis / drug effects*
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Blotting, Western
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Cell Line, Tumor
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Cell Proliferation / drug effects*
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Chenodeoxycholic Acid / analogs & derivatives
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Chenodeoxycholic Acid / chemical synthesis
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Chenodeoxycholic Acid / pharmacology*
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Colonic Neoplasms / metabolism
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Colonic Neoplasms / pathology
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DNA Fragmentation
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Glioblastoma / metabolism
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Glioblastoma / pathology
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Humans
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Lithocholic Acid / analogs & derivatives
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Lithocholic Acid / chemical synthesis
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Lithocholic Acid / pharmacology*
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Multiple Myeloma / metabolism
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Multiple Myeloma / pathology
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / genetics
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NF-kappa B / metabolism
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Neoplasms* / metabolism
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Neoplasms* / pathology
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Piperazines / chemical synthesis
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Piperazines / pharmacology*
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Signal Transduction
Substances
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Amides
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NF-kappa B
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Piperazines
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Chenodeoxycholic Acid
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Lithocholic Acid