Inhibition of cell growth and induction of apoptosis by acacetin in FaDu human pharyngeal carcinoma cells
강경록, 김재성, 김태현, 서정연, 박종현, 임진웅, 유선경, 김흥중, 신상훈, 박보람, 김춘성, 김도경,
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강경록 ( Kang Kyeong-Rok ) - Chosun University Institute of Dental Science
김재성 ( Kim Jae-Sung ) - Chosun University Institute of Dental Science
김태현 ( Kim Tae-Hyeon ) - Chosun University Institute of Dental Science
서정연 ( Seo Jeong-Yeon ) - Chosun University Institute of Dental Science
박종현 ( Park Jong-Hyun ) - Chosun University Institute of Dental Science
임진웅 ( Lim Jin-Woong ) - Chosun University Institute of Dental Science
유선경 ( Yu Sun-Kyoung ) - Chosun University Institute of Dental Science
김흥중 ( Kim Heung-Joong ) - Chosun University Institute of Dental Science
신상훈 ( Shin Sang-Hun ) - Chosun University Institute of Dental Science
박보람 ( Park Bo-Ram ) - Kyungwoon University College of Health and Welfare Department of Dental Hygiene
김춘성 ( Kim Chun-Sung ) - Chosun University Institute of Dental Science
김도경 ( Kim Do-Kyung ) - Chosun University Institute of Dental Science
Abstract
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.
키워드
Acacetin, Cell death, Apoptosis, Anticancer effect
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