Abstract
Heptaphylline derivatives are carbazoles in Clausena harmandiana, a medicinal plant that is utilized for headache, stomach ache, and other treatments of illness. The present study examined the effects of heptaphylline and 7-methoxyheptaphylline on apoptosis of human colon adenocarcinoma cells (HT-29 cell line). Quantification of cell viability was performed using cell proliferation assay (MTT assay) and of protein expression through immunoblotting. The results showed that only heptaphylline, but not 7-methoxyheptaphylline, significantly significantly activated cleaved of caspase-3 and poly (ADP-ribose) polymerase (PARP-1) which resulted in HT-29 cell death. We found that heptaphylline activated BH3 interacting-domain death agonist (Bid) and Bak, proapoptotic proteins. In contrast, it suppressed X-linked inhibitor-of-apoptosis protein (XIAP), Bcl-xL and survivin, inhibitors of apoptosis. In addition, heptaphylline inhibited activation of NF-κB/p65 (rel), a regulator of apoptotic regulating proteins by suppressing the activation of Akt and IKKα, upstream regulators of p65. The findings suggested that heptaphylline induces apoptosis in human colon adenocarcinoma cells .
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / metabolism*
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Apoptosis / drug effects*
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BH3 Interacting Domain Death Agonist Protein / drug effects
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BH3 Interacting Domain Death Agonist Protein / metabolism
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Carbazoles / pharmacology*
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Caspase 3 / drug effects
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Caspase 3 / metabolism
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Colonic Neoplasms / metabolism*
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HT29 Cells
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Humans
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I-kappa B Kinase / drug effects
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I-kappa B Kinase / metabolism
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Inhibitor of Apoptosis Proteins / drug effects
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Inhibitor of Apoptosis Proteins / metabolism
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Poly (ADP-Ribose) Polymerase-1
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Poly(ADP-ribose) Polymerases / drug effects
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Poly(ADP-ribose) Polymerases / metabolism
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Proto-Oncogene Proteins c-akt / drug effects*
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Proto-Oncogene Proteins c-akt / metabolism
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Signal Transduction / drug effects
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Survivin
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Transcription Factor RelA / drug effects*
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Transcription Factor RelA / metabolism
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X-Linked Inhibitor of Apoptosis Protein / drug effects
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X-Linked Inhibitor of Apoptosis Protein / metabolism
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bcl-2 Homologous Antagonist-Killer Protein / drug effects
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bcl-2 Homologous Antagonist-Killer Protein / metabolism
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bcl-X Protein / drug effects
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bcl-X Protein / metabolism
Substances
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7-methoxyheptaphylline
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BAK1 protein, human
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BCL2L1 protein, human
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BH3 Interacting Domain Death Agonist Protein
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BID protein, human
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BIRC5 protein, human
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Carbazoles
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Inhibitor of Apoptosis Proteins
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Survivin
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Transcription Factor RelA
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X-Linked Inhibitor of Apoptosis Protein
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XIAP protein, human
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bcl-2 Homologous Antagonist-Killer Protein
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bcl-X Protein
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heptaphylline
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PARP1 protein, human
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Poly (ADP-Ribose) Polymerase-1
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Poly(ADP-ribose) Polymerases
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Proto-Oncogene Proteins c-akt
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I-kappa B Kinase
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CASP3 protein, human
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Caspase 3