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Heptaphylline Induces Apoptosis in Human Colon Adenocarcinoma Cells through Bid and Akt/NF-κB (p65) Pathways

  • Boonyarat, Chantana (Faculty of Pharmaceutical Sciences, Khon Kaen University) ;
  • Yenjai, Chavi (Center of Natural Products Research Unit, Center for Innovation in Chemistry, Department of Chemistry, Faculty of Science, Khon Kaen University) ;
  • Vajragupta, Opa (Center for Excellence for Innovation in Drug Design and Discovery, Faculty of Pharmacy, Mahidol University) ;
  • Waiwut, Pornthip (Faculty of Pharmaceutical Sciences, Ubon Ratchathani University)
  • Published : 2015.01.06

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-${\kappa}B$/p65 (rel), a regulator of apoptotic regulating proteins by suppressing the activation of Akt and $IKK{\alpha}$, upstream regulators of p65. The findings suggested that heptaphylline induces apoptosis in human colon adenocarcinoma cells.

Keywords

Heptaphylline;colon adenocarcinoma cells;Bid;XIAP;Bcl-xL;Akt;p65

Acknowledgement

Supported by : Thailand Research Fund

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