• YAKHAK HOEJI
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• v.59 no.1
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• pp.17-22
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• 2015

In this study, we examined the effect of acacetin on the apoptosis induction of HeLa human cervical cancer cells. The results showed that acacetin inhibited the cell viability and induced apoptosis, leading to PARP cleavage and activation of caspase-9, -3, and -7. Moreover, acacetin-induced apoptosis was attenuated by a broad caspase inhibitor, z-VAD-fmk. Also, acacetin resulted in a loss of mitochondria membrane potential. Taken together, our results demonstrate that the induction of apoptosis by acacetin in HeLa cells is associated with caspase activation via the mitochondria pathway.

• International Journal of Oral Biology
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• v.45 no.3
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• pp.107-114
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• 2020

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.

• Molecules and Cells
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• v.24 no.1
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• pp.95-104
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• 2007

The mechanism of acacetin-induced apoptosis of human breast cancer MCF-7 cells was investigated. Acacetin caused 50% growth inhibition ($IC_{50}$) of MCF-7 cells at $26.4{\pm}0.7{\mu}M$ over 24 h in the MTT assay. Apoptosis was characterized by DNA fragmentation and an increase of sub-G1 cells and involved activation of caspase-7 and PARP (poly-ADP-ribose polymerase). Maximum caspase 7 activity was observed with $100{\mu}M$ acacetin for 24 h. Caspase 8 and 9 activation cascades mediated the activation of caspase 7. Acacetin caused a reduction of Bcl-2 expression leading to an increase of the Bax:Bcl-2 ratio. It also caused a loss of mitochondrial membrane potential that induced release of cytochrome c and apoptosis inducing factor (AIF) into the cytoplasm, enhancing ROS generation and subsequently resulting in apoptosis. Pretreatment of cells with N-acetylcysteine (NAC) reduced ROS generation and cell growth inhibition, and pretreatment with NAC or a caspase 8 inhibitor (Z-IETD-FMK) inhibited the acacetin-induced loss of mitochondrial membrane potential and release of cytochrome c and AIF. Stress-activated protein kinase/c-Jun $NH_4$-terminal kinase 1/2 (SAPK/JNK1/2) and c-Jun were activated by acacetin but extracellular-regulated kinase 1/2 (Erk1/2) nor p38 mitogen-activated protein kinase (MAPK) were not. Our results show that acacetin-induced apoptosis of MCF-7 cells is mediated by caspase activation cascades, ROS generation, mitochondria-mediated cell death signaling and the SAPK/JNK1/2-c-Jun signaling pathway, activated by acacetin-induced ROS generation.

• Journal of Microbiology and Biotechnology
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• v.30 no.10
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• pp.1567-1573
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• 2020

Ultraviolet (UV) is one of the major factors harmful to skin health. Irradiation with ultraviolet accelerates the decline of skin function, causing the skin to have deep wrinkles, dryness, decreased procollagen production, and degradation of collagen. Novel materials are needed to prevent the aging of the skin by blocking the effects of UV. Safflower seed oil (Charthamus tinctorius L., SSO) contains significantly high levels of unsaturated fatty acids and phytochemicals. SSO has been traditionally used in China, Japan, and Korea to improve skin and hair. Our objective in this study was to determine the effect of SSO and its active compound acacetin on UVB-induced skin photoaging in HaCaT cells and human dermal fibroblasts (HDF). SSO inhibited UVB-induced matrix metalloproteinase-1 (MMP-1) at both protein and mRNA levels in HaCaT cells and HDF. MMP-1 is known to play important roles in collagen degradation and wrinkle formation. Acacetin, a type of flavonoid, is present in SSO. Similar to SSO, acacetin also inhibited UVB-induced MMP-1 protein and mRNA levels in HaCaT cells and HDF. MMP-1 mRNA is primarily regulated by the mitogen-activated kinase (MAPK) signaling pathway. Acacetin regulated the phosphorylation of JNK1/2 and c-jun, but did not inhibit the phosphorylation of ERK1/2, p38 and AKT. Taken together, these results indicate that SSO and its active compound acacetin can prevent UVB-induced MMP-1 expression, which leads to skin photoaging, and may therefore have therapeutic potential as an anti-wrinkle agent to improve skin health.

• YAKHAK HOEJI
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• v.11 no.1_2
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• pp.7-16
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• 1967

A yellowish microneedles, $C_{28}$ H$_{32}$ $O_{14}$ ${\cdot}$ I$_{1}$/$_2$, H$_{2}$O, m.p.262-$4^{\circ}$ , [${\alpha}$$_{D}^{20}$= -71,$43^{\circ}$(C = 0.42, pyridine), its acetate m.p.123-5.deg., were obtained in 0.3% yield from the leaves of Chrysanthemum sibiricum F$_{ISCHER}$. This substance is insoluble in water and the usual organic solvents except pyridine and ethylene glycol and, is not decomposed by dilute mineral acids but undergoes decomposition on being boiled in 60% H$_{2}$SO$_{4}$ or 35% HCl, giving one moel each of acacetin, glucose and rhamnose. It was not hydrolysed with a rhamnodiastase preparation obtained from the seeds of Rhamnus koraiensis. After permethylation of it, the uncrystallized product was hydrolysed and apigenin-5,4'-dimethyl ehter, m.p.$262^{\circ}$ was obtained, indicating that the disaccharide residue is at the 7 position of acacetin. Partial hydrolysis of this acacetin-7-rhamnoglucoside in cyclohexanol with formic acid gave acacetin-7-glucoside, m.p.246.deg. and rutinose, identifying them with authentic specimen on a paper chromatography. It was thus identified as linarin(acacetin-7-rutinoside) by means of mixed fusion, of paper partition chromatography and of its derivatives. Zemplen and Bognar suggested that the glucosidic linkage of linarin is .betha. by means of synthesis of this substance. But there is no evidence whether it is hydrolysed by emulsin or maltase or not. Linarin itself was not hydrolysed by an emulsin existing in the seed of Apricot or a maltase, but acacetin-7-glucoside(tilianin) which obtained from linarin gave acacetin and glucose on hydrolysis with the same emulsin and accordingly the glucosidic linkages of linarin and tilianin are thus regarded as ${\beta}$.

• Journal of Applied Biological Chemistry
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• v.59 no.4
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• pp.357-360
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• 2016

Chrysanthemum morifolium flowers were extracted with 80 % aqueous MeOH, and the concentrated extract was partitioned into EtOAc, n-butyl alcohol (n-BuOH), and water fractions. The repeated silica gel and octadecyl silica gel column chromatographies for the EtOAc and n-BuOH fractions led to isolation of four flavonoids. The chemical structures of the compounds were determined as acacetin (1), apigenin (2), apigenin-7-O-${\beta}$-$\small{D}$-glucopyanoside (3), acacetin-7-O-${\beta}$-$\small{D}$-glucopyranoside (4) based on spectroscopic data analyses including nuclear magnetic resonance, mass spectrometry, and infrared spectrometry.

• Food Science and Biotechnology
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• v.16 no.2
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• pp.265-269
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• 2007

There is significant interest in finding new sources of acetylcholinesterase (AChE) inhibitors for use in treating Alzheimer's disease, since only a few AChE inhibitors are available for clinical use, such as galanthamine, physostigmine, and tacrine. The ethanol extract of Chrysanthemum indicum Linne flowers was analyzed and found to markedly decrease AChE activity. Acaciin and $acacetin-7-O-{\beta}-D-galactopyranoside$ were identified as the active compounds responsible for the AChE inhibition by using an activity-guided fractionation strategy. The relationship between structure and activity for five flavonoids (acaciin, $acacetin-7-O-{\beta}-D-galactopyranoside$, luteolin, and two other commercially available flavonoids, i.e., apigenin and acacetin) was also investigated, revealing that the presence of methoxy groups at C-4' in the B ring and a sugar at O-7 in ring A appear to be essential for the inhibition of AChE.

• Preventive Nutrition and Food Science
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• v.4 no.4
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• pp.221-225
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• 1999

Antioxidative compounds contained in roasted safflower seeds were investigated. Six phenolic compounds, N-feruloylserotonin, N-(p-coumaroyl) serotonin, matairesinol, 8'-hydroxyarctigenin, acacetin 7-Ο-β-D-glucoside(tilianine) and acacetin were isolated and identified from the extract of seeds. The inhibitory effects of six phenolic compounds on 1,1-dipheny1-2-picrylhydrazyl(DPPH) radical and lipid peroxidation induced by H₂O₂/FeSO₄in rat liver microsomes were determined. Two serotonins showed more potent DPPH radical scavenging activity, and a stronger inhibitory effect on the lipid peroxidation than that of α-tocopherol. In addition, acacetin and matairesinol also considerably inhibited lipid peroxidation, while 2-hydroxy-arctigenin and tilianine were inactive. These results suggest that phenolic compounds, including serotonins, lignans and flavonoids in the roasted safflower seeds can be used as potential dietary natural antioxidants.

• Journal of Microbiology and Biotechnology
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• v.27 no.1
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• pp.197-205
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• 2017

Exposure of Jurkat T cell clone (J/Neo cells) to acacetin (5,7-dihydroxy-4'-methoxyflavone), which is present in barnyard millet (Echinochloa esculenta (A. Braun)) grains, caused cytotoxicity, enhancement of apoptotic $sub-G_1$ rate, Bak activation, loss of mitochondrial membrane potential (${\Delta}{\Psi}m$), activation of caspase-9 and caspase-3, degradation of poly(ADP-ribose) polymerase, and FITC-Annexin V-stainable phosphatidylserine exposure on the external surface of the cytoplasmic membrane without accompanying necrosis. These apoptotic responses were abrogated in Jurkat T cell clone (J/Bcl-xL) overexpressing Bcl-xL. Under the same conditions, cellular autophagic responses, including suppression of the Akt-mTOR pathway and p62/SQSTM1 down-regulation, were commonly detected in J/Neo and J/Bcl-xL cells; however, formation of acridine orange-stainable acidic vascular organelles, LC3-I/II conversion, and Beclin-1 phosphorylation (Ser-15) were detected only in J/Neo cells. Correspondingly, concomitant treatment with the autophagy inhibitor (3-methyladenine or LY294002) appeared to enhance acacetin-induced apoptotic responses, such as Bak activation, ${\Delta}{\Psi}m$ loss, activation of caspase-9 and caspase-3, and apoptotic $sub-G_1$ accumulation. This indicated that acacetin could induce apoptosis and cytoprotective autophagy in Jurkat T cells simultaneously. Together, these results demonstrate that acacetin induces not only apoptotic cell death via activation of Bak, loss of ${\Delta}{\Psi}m$, and activation of the mitochondrial caspase cascade, but also cytoprotective autophagy resulting from suppression of the Akt-mTOR pathway. Furthermore, pharmacologic inhibition of the autophagy pathway augments the activation of Bak and resultant mitochondrial damage-mediated apoptosis in Jurkat T cells.

• Korean Journal of Pharmacognosy
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• v.31 no.1
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• pp.105-108
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• 2000

Impatiens textori Miquel (Balsaminaceae) is an annual plant growing in most parts of Korea. The herb of this plant has been used for the external application of snake poison and the bruise. Previous investigations conducted with the herbs have demonstrated it to contain three flavones and three flavone glycosides. Continuing to previous reports, quercetin, kaempferol and acacetin $7-O-{\beta}-D-glucoside$ were isolated from the herbs of this plant.