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http://dx.doi.org/10.7314/APJCP.2014.15.23.10483

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)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.23, 2015 , pp. 10483-10487 More about this Journal
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;
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1 Aouacheria A, Neel B, Bouaziz ZR, et al (2002). Carbazolequinone induction of caspase-dependent cell death in Src-overexpressing cells. Biochem Pharmacol, 64, 1605-16.   DOI
2 Chen X, Ding WX, Ni HM, et al (2006). Bid-independent mitochondrial activation in tumor necrosis factor alphainduced apoptosis and liver injury. Mol Cell Biol, 27, 541-53.
3 Dai Y, Rahmani M, Dent P, et al (2005). Kinase 1 Activation Downregulation, and c-Jun N-terminal mediated by oxidative damage, XIAP leukemia cells through a process NF-kB activation potentiates apoptosis in inhibitor-induced RelA/p65 acetylation and blockade. Mol Cell Biol, 25, 5429.   DOI
4 Debatin KM, Krammer PH (2004). Death receptors in chemotherapy and cancer. Oncogene, 23, 2950-66.   DOI
5 Evan GI, Vousden KH (2001). Proliferation, cell cycle and apoptosis in cancer. Nature, 411, 342-8.   DOI
6 Ghobrial IM, Witzig TE, Adjei AA (2005). Targeting apoptosis pathways in cancer therapy. CA Cancer J Clin, 55, 178-94.   DOI
7 Hanahan D and Weinberg RA (2011). Hallmarks of cancer: the next generation. Cell, 144, 646-74.   DOI
8 Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell, 100, 57-70.   DOI
9 Ip SW, Lan SH, Lu HF, et al (2012). Capsaicin mediates apoptosis in human nasopharyngeal carcinoma NPC-TW 039 cells through mitochondrial depolarization and endoplasmic reticulum stress. Hum Exp Toxicol, 31, 539-49.   DOI
10 Ito C, Itoigawa M, Katsuno S, et al (2000). Chemical constituents of Clausena excavata: isolation and structure elucidation of novel furanone-coumarins with inhibitory effects for tumorpromotion. J Nat Prod, 63, 1218-24.   DOI   ScienceOn
11 Kantari C, Walczak H (2011) Caspase-8 and Bid: caught in the act between death receptors and mitochondria. Biochim Biophys Acta, 1813, 558-63.   DOI
12 Kim JH, Choi YW, Park C, et al (2010). Apoptosis induction of human leukemia U937 cells by gomisin N, a dibenzocyclooctadiene lignan, isolated from Schizandra chinensis Baill. Food Chem Toxicol, 48, 807-13.   DOI   ScienceOn
13 Millimouno FM, Dong J, Yang L, Li J, Li X (2014). Targeting apoptosis pathways in cancer and perspectives with natural compounds from mother nature. Cancer Prev Res, 7, 1081-107.   DOI
14 Korsmeyer SJ, Wei MC, Saito M, et al (2000). Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome C. Cell Death Differ, 7, 1166-73.   DOI
15 Liu J, Uematsu H, Tsuchida N, et al (2011). Essential role of caspase-8 in p53/p73-dependent apoptosis induced by etoposide in head and neck carcinoma cells. Mol Cancer, 31, 95.
16 Mendoza FJ, Espino PS, Cann KL, et al (2005). Anti-tumor chemotherapy utilizing peptide-based approaches- apoptotic pathways, kinases, and proteasome as targets. Arch Immunol Ther Exp, 53, 47-60.
17 Namba H, Saenko V, Yamashita S (2007). Nuclear factor-${\kappa}$B in thyroid carcinogenesis and progression: a novel therapeutic target for advanced thyroid cancer. Arq Bras Endocrinol Metab, 51, 843-51.   DOI
18 Okada H, Mak TW (2004). Pathways of apoptotic and nonapoptotic death in tumour cells. Nat Rev Cancer, 4, 592-603.   DOI
19 Pei Y, Xing D, Gao X, Liu L, Chen T (2007) Real-time monitoring full length bid interacting with Bax during TNFalpha-induced apoptosis. Apoptosis, 12, 1681-90.   DOI
20 Perez D, White E (2000). TNF-alpha signals apoptosis through a bid-dependent conformational change in Bax that is inhibited by E1B 19K. Mol Cell, 6, 53-63.   DOI
21 Shukla S, MacLennan GT, Fu P, et al (2004). Nuclear factorkappaB/p65 (Rel A) is constitutively activated in human prostate adenocarcinoma and correlates with disease progression. Neoplasia, 6, 390-400.   DOI
22 Thongthoom T, Promsuwan P, Yenjai C (2011). Synthesis and cytotoxic activity of the heptaphylline and 7-methoxyheptaphylline series. Eur J Med Chem, 9, 3755-61.
23 Songsiang U, Thongthoom T, Boonyarat C, Yenjai C (2011). Claurailas A-D, cytotoxic carbazole alkaloids from the roots of Clausena harmandiana. J Nat Prod, 74, 208-12.   DOI   ScienceOn
24 Stevenson HS, Fu SW, Pinzone JJ, et al (2007). BP1 transcriptionally activates bcl-2 and inhibits TNF-alphainduced cell death in MCF7 breast cancer cells. Breast Cancer Res, 9, 60.   DOI
25 Thongthoom T, Songsiang U, Phaosiri C, Yenjai C (2010). Biological activity of chemical constituents from Clausena harmandiana. Arch Pharm Res, 33, 675-80.   DOI   ScienceOn
26 Thorburn A, Behbakht K, Ford H (2008). TRAIL receptortargeted therapeu-tics: resistance mechanisms and strategies to avoid them. Drug Resist Updat, 11, 17-24.   DOI
27 Wangboonskul J, Yenjai C (2012). Antioxidant activity and cytotoxicity against cholangiocarcinoma of carbazoles and coumarins from Clausena harmandiana. Science Asia, 38, 75-81.   DOI
28 Wong RS (2011). Apoptosis in cancer: from pathogenesis to treatment 1-14. J Exp Clin Cancer Res, 30, 87.   DOI
29 Yenjai C, Sripontan S, Sriprajun P, et al (2000). Coumarins and carbazoles with antiplasmodial activity from Clausena harmandiana. Planta Med, 66, 277-9.   DOI