Inhibition of cell growth and induction of apoptosis by acacetin in FaDu human pharyngeal carcinoma cells

다국어 초록 (Multilingual Abstract)

Acacetin, which is present in damiana (Turnera diffusa ) and black locust (Robinia pseudoacacia ), has several
pharmacologic 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 aimed
to examine the effects of acacetin on cell growth and apoptosis induction in FaDu human pharyngeal carcinoma
cells. These were investigated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, Live/Dead
cell assay, 4′,6-diamidino-2-phenylindole dihydrochloride staining, caspase-3 and caspase-7 activation assay, and
immunoblotting in FaDu cells. Acacetin induced FaDu cell death in a dose-dependent manner, with an estimated
IC50 value of 41.9 µM, without affecting the viability of L-929 mouse fibroblasts as normal cells. Acacetin treatment
resulted 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 cells
was 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 upregulation
of the mitochondria-dependent pro-apoptotic proteins Bax and Badin FaDu cells after acacetin treatment. These
findings indicate that acacetin inhibits cell proliferation and induces apoptotic cell death in FaDu human pharyngeal
carcinoma cells via both the death receptor-mediated extrinsic apoptotic pathway and the mitochondria-mediated
intrinsic apoptotic pathway.