title: Heptaphylline induces apoptosis in human colon adenocarcinoma cells through bid and Akt/NF-κB (p65) pathways.
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 .
authors.affiliation: Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand E-mail : pwaiwut79@yahoo.com, phpornwa@ubu.ac.th.
authors.forename: Chantana
authors.initials: C
authors.lastname: Boonyarat
authors.forename: Chavi
authors.initials: C
authors.lastname: Yenjai
authors.forename: Opa
authors.initials: O
authors.lastname: Vajragupta
authors.forename: Pornthip
authors.initials: P
authors.lastname: Waiwut
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000187:drug effects / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000187:drug effects / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins / Q000187:drug effects / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077022:Survivin; D051996:Transcription Factor RelA / Q000187:drug effects* / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000187:drug effects / Q000378:metabolism; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000187:drug effects / Q000378:metabolism; D051020:bcl-X Protein / Q000187:drug effects / Q000378:metabolism
chemical_list: C557425:7-methoxyheptaphylline; C494772:BAK1 protein, human; C494811:BCL2L1 protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; C107489:BIRC5 protein, human; D002227:Carbazoles; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D051996:Transcription Factor RelA; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein; C557424:heptaphylline; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase; C505407:CASP3 protein, human; D053148:Caspase 3