7-hydroxyflavone and naringenin

Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers with a poor prognosis due to frequent lymph node metastasis and local invasion. A growing number of in vitro studies have been conducted on the potential anticancer activity of flavonoids in various cancer cell lines. However, the antimetastatic activities of flavones, one subclass of flavonoids, in human oral squamous carcinoma SCC-4 cells have not been understood clearly.. The present study investigated the effect of four flavones on invasion and migration of SCC-4 cells to find that 7-hydroxyflavanone, 5,6,7-trihydroxyflavanone, and 4',5,7-trihydroxyflavanone exerted a dose-dependent inhibitory effect on the invasion and migration of SCC-4 cells.. Results from zymography and Western blot showed that flavones treatment may decrease the expressions of matrix metalloproteinase (MMP)-2, urokinase plasminogen activator (u-PA) in a concentration-dependent manner, together with altered expression levels of their endogenous inhibitors, which are tissue inhibitor of metalloproteinase-2 (TIMP-2) and plasminogen activator inhibitor-1 (PAI-1). Furthermore, an in vivo chorioallantoic membrane (CAM) intravasation assay was also treated and analysed to reveal the antimetastatic effect.. Our data suggest that 7-hydroxyflavanone, 5,6,7-trihydroxyflavanone, and 4',5,7-trihydroxyflavanone could be applicable to be a potential antimetastatic agent of SCC-4 cells.

Topics: Analysis of Variance; Antineoplastic Agents, Phytogenic; Blotting, Western; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Survival; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Flavanones; Flavones; Flavonoids; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Plasminogen Activator Inhibitor 1; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Tongue Neoplasms; Urokinase-Type Plasminogen Activator

Flavonoids and related structures (e.g., flavones, isoflavones, flavanones, catechins) exert various biological effects, including anticarcinogenic, antioxidant and (anti-)estrogenic effects, and modulation of sex hormone homeostasis. A key enzyme in the synthesis of estrogens from androgens is aromatase (cytochrome P450 19; CYP19). We investigated the effects of various natural and synthetic flavonoids on the catalytic activity and promoter-specific expression of aromatase in H295R human adrenocortical carcinoma cells. Natural flavones were consistently more potent inhibitors than flavanones. IC(50) values for 7-hydroxyflavone, chrysin, and apigenin were 4, 7, and 20 microM, respectively; for the flavanones 7-hydroxyflavanone and naringenin the IC(50) values were 65 and 85 microM, respectively. The steroidal aromatase inhibitor (positive control) 4-hydroxyandrostenedione had an IC(50) of 20 nM. The inhibition by apigenin and naringenin coincided with some degree of cytotoxicity at 100 microM. The natural flavonoid derivative rotenone (IC(50) 0.3 microM) was the most potent aromatase inhibitor tested. Several synthetic flavonoid and structurally related quinolin-4-one analogs inhibited aromatase activity. The most potent inhibitor was 4'-tert-butyl-quinolin-4-one (IC(50) 2 microM), followed by two 2-pyridinyl-substituted alpha-naphthoflavones (IC(50)s 5 and >30 microM). The two 2-pyridinyl-substituted gamma-naphthoflavones consistently produced biphasic concentration-response curves, causing about 1.5-fold aromatase induction at concentrations below 1 microM and inhibition above that level (IC(50)s 7 and >30 microM). The natural flavone quercetin and isoflavone genistein induced aromatase activity 4- and 2.5-fold induction, respectively, at 10 microM. This coincided with increased intracellular cAMP concentrations and increased levels of the cAMP-dependent pII and to a lesser extent 1.3 promoter-specific aromatase transcripts. These results shed light on the structure-activity relationships for aromatase inhibition as well as mechanisms of induction in human H295R cells.

Topics: Adrenal Gland Neoplasms; Adrenocortical Carcinoma; Apigenin; Aromatase; Aromatase Inhibitors; Cell Line, Tumor; Dose-Response Relationship, Drug; Enzyme Induction; Flavanones; Flavonoids; Humans; Rotenone; Structure-Activity Relationship