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http://dx.doi.org/10.4196/kjpp.2022.26.6.447

Arctigenin induces caspase-dependent apoptosis in FaDu human pharyngeal carcinoma cells  

Kang, Kyeong-Rok (The Institute of Dental Science, Chosun University)
Kim, Jae-Sung (The Institute of Dental Science, Chosun University)
Lim, HyangI (The Institute of Dental Science, Chosun University)
Seo, Jeong-Yeon (The Institute of Dental Science, Chosun University)
Park, Jong-Hyun (The Institute of Dental Science, Chosun University)
Chun, Hong Sung (Department of Integrative Biological Sciences & BK21 FOUR Educational Research Group for Age-associated Disorder Control Technology, Chosun University)
Yu, Sun-Kyoung (The Institute of Dental Science, Chosun University)
Kim, Heung-Joong (The Institute of Dental Science, Chosun University)
Kim, Chun Sung (The Institute of Dental Science, Chosun University)
Kim, Do Kyung (The Institute of Dental Science, Chosun University)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.26, no.6, 2022 , pp. 447-456 More about this Journal
Abstract
The present study was carried out to investigate the effect of Arctigenin on cell growth and the mechanism of cell death elicited by Arctigenin were examined in FaDu human pharyngeal carcinoma cells. To determine the apoptotic activity of Arctigenin in FaDu human pharyngeal carcinoma cells, cell viability assay, DAPI staining, caspase activation analysis, and immunoblotting were performed. Arctigenin inhibited the growth of cells in a dose-dependent manner and induced nuclear condensation and fragmentation. Arctigenin-treated cells showed caspase-3/7 activation and increased apoptosis versus control cells. FasL, a death ligand associated with extrinsic apoptotic signaling pathways, was up-regulated by Arctigenin treatment. Moreover, caspase-8, a part of the extrinsic apoptotic pathway, was activated by Arctigenin treatments. Expressions of anti-apoptotic factors such as Bcl-2 and Bcl-xL, components of the mitochondria-dependent intrinsic apoptosis pathway, significantly decreased following Arctigenin treatment. The expressions of pro-apoptotic factors such as BAX, BAD and caspase-9, and tumor suppressor -53 increased by Arctigenin treatments. In addition, Arctigenin activated caspase-3 and poly (ADP-ribose) polymerase (PARP) induced cell death. Arctigenin also inhibited the proliferation of FaDu cells by the suppression of p38, NF-κB, and Akt signaling pathways. These results suggest that Arctigenin may inhibit cell proliferation and induce apoptotic cell death in FaDu human pharyngeal carcinoma cells through both the mitochondria-mediated intrinsic pathway and the death receptor-mediated extrinsic pathway.
Keywords
Apoptosis; Arctigenin; Caspase-dependent; Human pharyngeal carcinoma;
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1 Kluck RM, Martin SJ, Hoffman BM, Zhou JS, Green DR, Newmeyer DD. Cytochrome c activation of CPP32-like proteolysis plays a critical role in a Xenopus cell-free apoptosis system. EMBO J. 1997;16:4639-4649.   DOI
2 Kroemer G, Reed JC. Mitochondrial control of cell death. Nat Med. 2000;6:513-519.   DOI
3 Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V, Ross AJ, Roth KA, MacGregor GR, Thompson CB, Korsmeyer SJ. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science. 2001;292:727-730.   DOI
4 Reed JC. Apoptosis-regulating proteins as targets for drug discovery. Trends Mol Med. 2001;7:314-319.   DOI
5 Punia R, Raina K, Agarwal R, Singh RP. Acacetin enhances the therapeutic efficacy of doxorubicin in non-small-cell lung carcinoma cells. PLoS One. 2017;12:e0182870.   DOI
6 Yang Z, Liu N, Huang B, Wang Y, Hu Y, Zhu Y. [Effect of antiinfluenza virus of Arctigenin in vivo]. Zhong Yao Cai. 2005;28:1012-1014. Chinese.
7 Tsai WJ, Chang CT, Wang GJ, Lee TH, Chang SF, Lu SC, Kuo YC. Arctigenin from Arctium lappa inhibits interleukin-2 and interferon gene expression in primary human T lymphocytes. Chin Med. 2011;6:12.   DOI
8 Lee JY, Kim CJ. Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan, inhibits type I-IV allergic inflammation and proinflammatory enzymes. Arch Pharm Res. 2010;33:947-957.   DOI
9 He Y, Fan Q, Cai T, Huang W, Xie X, Wen Y, Shi Z. Molecular mechanisms of the action of arctigenin in cancer. Biomed Pharmacother. 2018;108:403-407.   DOI
10 Kim JS, Cho IA, Kang KR, Lim H, Kim TH, Yu SK, Kim HJ, Lee SA, Moon SM, Chun HS, Kim CS, Kim DK. Reversine induces caspasedependent apoptosis of human osteosarcoma cells through extrinsic and intrinsic apoptotic signaling pathways. Genes Genomics. 2019;41:657-665.   DOI
11 Pezzuto F, Buonaguro L, Caponigro F, Ionna F, Starita N, Annunziata C, Buonaguro FM, Tornesello ML. Update on head and neck cancer: current knowledge on epidemiology, risk factors, molecular features and novel therapies. Oncology. 2015;89:125-136.   DOI
12 Han YH, Kee JY, Kim DS, Mun JG, Jeong MY, Park SH, Choi BM, Park SJ, Kim HJ, Um JY, Hong SH. Arctigenin inhibits lung metastasis of colorectal cancer by regulating cell viability and metastatic phenotypes. Molecules. 2016;21:1135.   DOI
13 Yue J, Lopez JM. Understanding MAPK signaling pathways in apoptosis. Int J Mol Sci. 2020;21:2346.   DOI
14 Royuela M, Arenas MI, Bethencourt FR, Sanchez-Chapado M, Fraile B, Paniagua R. Regulation of proliferation/apoptosis equilibrium by mitogen-activated protein kinases in normal, hyperplastic, and carcinomatous human prostate. Hum Pathol. 2002;33:299-306.   DOI
15 Kalavrezos N, Scully C. Mouth cancer for clinicians. Part 2: epidemiology. Dent Update. 2015;42:354-356, 358-359.   DOI
16 Sun F, Li D, Wang C, Peng C, Zheng H, Wang X. Acacetin-induced cell apoptosis in head and neck squamous cell carcinoma cells: evidence for the role of muscarinic M3 receptor. Phytother Res. 2019;33:1551-1561.   DOI
17 Kundu SK, Nestor M. Targeted therapy in head and neck cancer. Tumour Biol. 2012;33:707-721.   DOI
18 Todd R, Donoff RB, Wong DT. The molecular biology of oral carcinogenesis: toward a tumor progression model. J Oral Maxillofac Surg. 1997;55:613-623; discussion 623-625.   DOI
19 Links M, Lewis C. Chemoprotectants: a review of their clinical pharmacology and therapeutic efficacy. Drugs. 1999;57:293-308.   DOI
20 Rahman MA, Hannan MA, Dash R, Rahman MH, Islam R, Uddin MJ, Sohag AAM, Rahman MH, Rhim H. Phytochemicals as a complement to cancer chemotherapy: pharmacological modulation of the autophagy-apoptosis pathway. Front Pharmacol. 2021;12:639628.   DOI
21 Sak K. Chemotherapy and dietary phytochemical agents. Chemother Res Pract. 2012;2012:282570.
22 Wang X, Zhang H, Chen X. Drug resistance and combating drug resistance in cancer. Cancer Drug Resist. 2019;2:141-160.
23 Creagh EM, Conroy H, Martin SJ. Caspase-activation pathways in apoptosis and immunity. Immunol Rev. 2003;193:10-21.   DOI
24 Tone S, Sugimoto K, Tanda K, Suda T, Uehira K, Kanouchi H, Samejima K, Minatogawa Y, Earnshaw WC. Three distinct stages of apoptotic nuclear condensation revealed by time-lapse imaging, biochemical and electron microscopy analysis of cell-free apoptosis. Exp Cell Res. 2007;313:3635-3644.   DOI
25 Tompkins KD, Thorburn A. Regulation of apoptosis by autophagy to enhance cancer therapy. Yale J Biol Med. 2019;92:707-718.
26 Park MG, Kim JS, Park SY, Lee SA, Kim HJ, Kim CS, Kim JS, Chun HS, Park JC, Kim DK. MicroRNA-27 promotes the differentiation of odontoblastic cell by targeting APC and activating Wnt/β-catenin signaling. Gene. 2014;538:266-272.   DOI
27 Jiang Y, Liu J, Hong W, Fei X, Liu R. Arctigenin inhibits glioblastoma proliferation through the AKT/mTOR pathway and induces autophagy. Biomed Res Int. 2020;2020:3542613.
28 Yang S, Ma J, Xiao J, Lv X, Li X, Yang H, Liu Y, Feng S, Zhang Y. Arctigenin anti-tumor activity in bladder cancer T24 cell line through induction of cell-cycle arrest and apoptosis. Anat Rec (Hoboken). 2012;295:1260-1266.   DOI
29 Wang HQ, Jin JJ, Wang J. Arctigenin enhances chemosensitivity to cisplatin in human nonsmall lung cancer H460 cells through downregulation of survivin expression. J Biochem Mol Toxicol. 2014;28:39-45.   DOI
30 Maxwell T, Chun SY, Lee KS, Kim S, Nam KS. The anti-metastatic effects of the phytoestrogen arctigenin on human breast cancer cell lines regardless of the status of ER expression. Int J Oncol. 2017;50:727-735.   DOI
31 Hadden JW. The immunopharmacology of head and neck cancer: an update. Int J Immunopharmacol. 1997;19:629-644.   DOI
32 Ray RS, Agrawal N, Sharma A, Hans RK. Use of L-929 cell line for phototoxicity assessment. Toxicol In Vitro. 2008;22:1775-1781.   DOI
33 Herrnring C, Reimer T, Jeschke U, Makovitzky J, Kruger K, Gerber B, Kabelitz D, Friese K. Expression of the apoptosis-inducing ligands FasL and TRAIL in malignant and benign human breast tumors. Histochem Cell Biol. 2000;113:189-194.   DOI
34 Alfarouk KO, Stock CM, Taylor S, Walsh M, Muddathir AK, Verduzco D, Bashir AH, Mohammed OY, Elhassan GO, Harguindey S, Reshkin SJ, Ibrahim ME, Rauch C. Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp. Cancer Cell Int. 2015;15:71.   DOI
35 Kaufmann SH, Earnshaw WC. Induction of apoptosis by cancer chemotherapy. Exp Cell Res. 2000;256:42-49.   DOI
36 Gao Q, Yang M, Zuo Z. Overview of the anti-inflammatory effects, pharmacokinetic properties and clinical efficacies of arctigenin and arctiin from Arctium lappa L. Acta Pharmacol Sin. 2018;39:787-801.   DOI
37 Yao X, Li G, Lu C, Xu H, Yin Z. Arctigenin promotes degradation of inducible nitric oxide synthase through CHIP-associated proteasome pathway and suppresses its enzyme activity. Int Immunopharmacol. 2012;14:138-144.   DOI
38 Kang HS, Lee JY, Kim CJ. Anti-inflammatory activity of arctigenin from Forsythiae Fructus. J Ethnopharmacol. 2008;116:305-312.   DOI
39 Lu Z, Cao S, Zhou H, Hua L, Zhang S, Cao J. Mechanism of arctigenin-induced specific cytotoxicity against human hepatocellular carcinoma cell lines: Hep G2 and SMMC7721. PLoS One. 2015;10:e0125727.   DOI
40 Hensley P, Mishra M, Kyprianou N. Targeting caspases in cancer therapeutics. Biol Chem. 2013;394:831-843.   DOI
41 Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45:309-316.   DOI
42 Rettig EM, D'Souza G. Epidemiology of head and neck cancer. Surg Oncol Clin N Am. 2015;24:379-396.   DOI
43 Sacks PG. Cell, tissue and organ culture as in vitro models to study the biology of squamous cell carcinomas of the head and neck. Cancer Metastasis Rev. 1996;15:27-51.   DOI
44 Goldar S, Khaniani MS, Derakhshan SM, Baradaran B. Molecular mechanisms of apoptosis and roles in cancer development and treatment. Asian Pac J Cancer Prev. 2015;16:2129-2144.   DOI