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KMID : 0848120200450030107
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International Journal of Oral Biology
2020 Volume.45 No. 3 p.107 ~ p.114
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Inhibition of cell growth and induction of apoptosis by acacetin in FaDu human pharyngeal carcinoma cells
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Kang Kyeong-Rok
Kim Jae-Sung
Kim Tae-Hyeon
Seo Jeong-Yeon
Park Jong-Hyun
Lim Jin-Woong
Yu Sun-Kyoung
Kim Heung-Joong
Shin Sang-Hun
Park Bo-Ram
Kim Chun-Sung
Kim Do-Kyung
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Abstract
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Acacetin, which is present in damiana (Turnera diffusa ) and black locust (Robinia pseudoacacia ), has severalpharmacologic activities such as antioxidant, anti-inflammatory, and anti-proliferative effects on cancer cells. However, the effect of acacetin on head and neck cancers has not been clearly established. This study aimedto examine the effects of acacetin on cell growth and apoptosis induction in FaDu human pharyngeal carcinomacells. These were investigated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, Live/Deadcell assay, 4′,6-diamidino-2-phenylindole dihydrochloride staining, caspase-3 and caspase-7 activation assay, andimmunoblotting in FaDu cells. Acacetin induced FaDu cell death in a dose-dependent manner, with an estimatedIC50 value of 41.9 μM, without affecting the viability of L-929 mouse fibroblasts as normal cells. Acacetin treatmentresulted in nuclear condensation in the FaDu cells. It promoted the proteolytic cleavage of procaspase-3, -7, -8, and-9 with increasing amounts of the cleaved caspase isoforms in FaDu cells. Acacetin-induced apoptosis in FaDu cellswas mediated by the expression of Fas and activation of caspase-8, caspase-3, and poly (ADP-ribose) polymerase. Immunoblotting showed downregulation of the anti-apoptotic mitochondrial proteins Bcl-2 and Bcl-xL, but upregulationof the mitochondria-dependent pro-apoptotic proteins Bax and Badin FaDu cells after acacetin treatment. Thesefindings indicate that acacetin inhibits cell proliferation and induces apoptotic cell death in FaDu human pharyngealcarcinoma cells via both the death receptor-mediated extrinsic apoptotic pathway and the mitochondria-mediatedintrinsic apoptotic pathway.
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KEYWORD
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Acacetin, Cell death, Apoptosis, Anticancer effect
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