Abstract
The plant sterol guggulsterone has recently been shown to have anti-tumorigenic potential. This study was designed to investigate the anti-tumor efficacy of guggulsterone and to elucidate its molecular mechanisms in colon cancer. Guggulsterone significantly increased apoptosis in HT-29 cells by activating caspases-3 and -8. Furthermore, guggulsterone decreased cIAP-1, cIAP-2, and Bcl-2 levels and increased the levels of truncated Bid, Fas, p-JNK, and p-c-Jun. The size of HT-29 xenograft tumors in guggulsterone-treated mice was significantly smaller than of the size of tumors in control mice. The present study suggests a potential therapeutic use for this compound in the treatment of colorectal cancer.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents, Phytogenic / pharmacology*
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Apoptosis / drug effects*
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BH3 Interacting Domain Death Agonist Protein / metabolism
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Baculoviral IAP Repeat-Containing 3 Protein
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Caspase 3 / metabolism
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Caspase 9 / metabolism
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Cell Proliferation / drug effects*
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Colorectal Neoplasms / drug therapy*
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Colorectal Neoplasms / metabolism
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Colorectal Neoplasms / pathology
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Dose-Response Relationship, Drug
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Enzyme Activation
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HT29 Cells
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Humans
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Inhibitor of Apoptosis Proteins / metabolism
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JNK Mitogen-Activated Protein Kinases / metabolism
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Male
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Mice
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Mice, Nude
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Phosphorylation
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Pregnenediones / pharmacology*
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Proto-Oncogene Proteins c-jun / metabolism
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Time Factors
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Ubiquitin-Protein Ligases
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Xenograft Model Antitumor Assays
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fas Receptor / metabolism
Substances
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Antineoplastic Agents, Phytogenic
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BH3 Interacting Domain Death Agonist Protein
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BID protein, human
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FAS protein, human
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Inhibitor of Apoptosis Proteins
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Pregnenediones
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Proto-Oncogene Proteins c-bcl-2
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Proto-Oncogene Proteins c-jun
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fas Receptor
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pregna-4,17-diene-3,16-dione
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BIRC3 protein, human
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Baculoviral IAP Repeat-Containing 3 Protein
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Ubiquitin-Protein Ligases
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JNK Mitogen-Activated Protein Kinases
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CASP3 protein, human
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CASP9 protein, human
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Caspase 3
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Caspase 9