Arctigenin induces caspase-dependent apoptosis in FaDu human pharyngeal carcinoma cells
Kyeong-Rok Kang1, Jae-Sung Kim1, HyangI Lim1, Jeong-Yeon Seo1, Jong-Hyun Park1, Hong Sung Chun2, Sun-Kyoung Yu1, Heung-Joong Kim1, Chun Sung Kim1, and Do Kyung Kim1,*
1The Institute of Dental Science, Chosun University, 2Department of Integrative Biological Sciences & BK21 FOUR Educational Research Group for Ageassociated Disorder Control Technology, Chosun University, Gwangju 61452, Korea
Author contributions: K.R.K., H.I.L., J.Y.S., J.H.P., and D.K.K. contributed to the cell based experimental design and collected the data. J.S.K., H.J.K., H.S.C., S.K.Y., and C.S.K. contributed to the data analysis and interpretation. K.R.K. and D.K.K. did the writing and revisions of manuscript.
Received: March 18, 2022; Revised: August 29, 2022; Accepted: September 19, 2022
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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