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BackgroundTriple-negative breast cancer (TNBC) has a high risk of relapse and there are few chemotherapy options. Although 5-hydroxytryptamine (5-HT, serotonin) signaling pathways have been suggested as potential targets for anti-cancer drug development, the mechanism responsible for the action of 5-HT in TNBC remains unknown.MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to measure mRNA and protein levels, respectively. Cell proliferation was measured using CellTiter 96 Aqueous One Solution. siRNA transfection was used to assess involvement of genes in cancer invasion, which were identified by Matrigel transwell invasion assay. Levels of 5-HT and vascular endothelial growth factor (VEGF) were measured using ELISA kits. Chick chorioallantoic membrane (CAM) assay and mouse tumor model were used to investigate the in vivo effects of SB269970, a 5-HT7 receptor antagonist, and BJ-1113, a novel synthetic compound.ResultsTNBC cell lines (MDA-MB-231, HCC-1395, and Hs578T) expressed higher levels of tryptophan hydroxylase 1 (TPH1) than hormone-responsive breast cancer cell lines (MCF-7 and T47D). In MDA-MB-231 cells, 5-HT promoted invasion and proliferation via 5-HT7 receptor, and interestingly, the stimulatory effect of 5-HT on MDA-MB-231 cell invasion was stronger than its effect on proliferation. Likewise, downstream signaling pathways of 5-HT7 differed during invasion and proliferation, that is, Gα-activated cAMP and Gβγ-activated kinase signaling during invasion, and Gβγ-activated PI3K/Akt signaling during proliferation. Also, 5-HT increased the protein expressions of TPH1 and VEGF in MDA-MB-231 cells. These results provide insight of the stimulatory effect of 5-HT on breast cancer progression; 5-HT was found to act more strongly during the first stage of metastasis (during invasion and migration) than during the later proliferative phase after local invasion. Interestingly, these actions of 5-HT were inhibited by BJ-1113, a 6-amino-2,4,5-trimethylpyridin-3-ol analog. BJ-1113 blocked intracellular signaling pathways initiated by 5-HT7 receptor activation, and exhibited anti-proliferative and anti-invasive activities against MDA-MB-231 cells. Furthermore, the inhibitory effect of BJ-1113 against MDA-MB-231 tumor growth was greater than that of SB269970, a 5-HT7 receptor antagonist.Conclusions5-HT7 receptor which mediates 5-HT-induced cancer progression is a potential therapeutic target in TNBC, and BJ-1113 offers a novel scaffold for the development of anti-cancer agents against TNBC.

The present study aimed to evaluate the contribution of anthocyanin composition to the total antioxidant capacity (TAC) of berries having different anthocyanin composition; blackberry, black currant, and blueberry. Blackberry demonstrated the highest TAC, while it had the lowest total anthocyanin content among the three berries in both of the phenolic extract and anthocyanin fractions. On the other hand, black currant had the highest total anthocyanin content, but the lowest TAC. Cyanidin-3-O-glucoside (cya-3-glc) accounted for 94% of blackberry anthocyanins, and as one of the strongest antioxidants present in these three berries, it substantially contributed to the TAC of blackberry anthocyanin fraction (96.0%). Delphinidin-3-O-rutinoside and cyanidin-3-O-rutinoside in black currant had lower antioxidant capacities compared with delphinin-3-O-glucoside and cya-3-glc, resulting in its lowest TAC among berry anthocyanin fractions examined. Malvidin derivatives, major anthocyanins of blueberry, had considerably lower antioxidant capacity than other anthocyanidin derivatives, such as cyanidin or delphinidin, resulting in lower TAC of blueberry compared with blackberry. Our findings indicate that anthocyanin composition as well as the antioxidant capacity of individual anthocyanins contributes to the TAC of berries rich in distinct anthocyanins.

It is known that flavonoids in sprouts were accumulated more under light irradiation than under dark. Light source affecting flavonoid accumulation in sprouts is still investigating. We evaluated the effects of light sources, including red, blue and fluorescent lights, on the flavonoid accumulation and antioxidant activity in common buckwheat sprouts. Experimental results showed that blue light significantly enhanced the contents of -glycosylflavones, including orientin, vitexin and their isomers, and rutin and a rutin isomer. Sprouts grown under blue light exhibit also the highest total phenolics and total flavonoids as well as the highest antioxidant activities. It was found that isoorientin is the highest antioxidant flavonoid whereas numerous former studies suggested that rutin is a typical antioxidant compound in common buckwheat. These results indicated that blue light could be applied for enhancing not only the content of flavonoids but also antioxidant activity in common buckwheat sprouts.

3-Pyridinols bearing amine substitution para to the hydroxylic moiety have previously been shown to inhibit lipid peroxidation more effectively than typical phenolic antioxidants, for example, α-tocopherol. We report here high-yielding, large-scale syntheses of mono- and bicyclic aminopyridinols from pyridoxine hydrochloride (i.e., vitamin B(6)). This approach provides straightforward, scaleable access to novel, potent, molecular scaffolds whose antioxidant properties have been investigated in homogeneous solutions and in liposomal vesicles. These molecular aggregates mimic cell membranes that are the targets of oxidative damage in vivo.

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Buckwheat sprouts have been widely consumed all around world due to their great abundance of bioactive compounds. In this study, the anti-inflammatory effects of flavonoid-rich common buckwheat sprout (CBS) and tartary buckwheat sprout (TBS) extracts were evaluated in lipopolysaccharide- (LPS-) stimulated RAW 264.7 murine macrophages and primary peritoneal macrophages from male BALB/c mice. Based on the reversed-phase HPLC analysis, the major flavonoids in CBS were determined to be C-glycosylflavones (orientin, isoorientin, vitexin, and isovitexin), quercetin-3-O-robinobioside, and rutin, whereas TBS contained only high amounts of rutin. The TBS extract exhibited higher inhibitory activity as assessed by the production of proinflammatory mediators such as nitric oxide and cytokines including tumor necrosis factor-α, interleukin- (IL-) 6, and IL-12 in LPS-stimulated RAW 264.7 macrophages than CBS extract. In addition, TBS extract suppressed nuclear factor-kappa B activation by preventing inhibitor kappa B-alpha degradation and mitogen-activated protein kinase phosphorylation in LPS-stimulated RAW 264.7 macrophages. Moreover, the TBS extract markedly reduced LPS-induced cytokine production in peritoneal macrophages. Taken together, these findings suggest that TBS extract can be a potential source of anti-inflammatory agents that may influence macrophage-mediated inflammatory disorders.

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