ABSTRACT
Tetrahydrocurcumin (THC) has been shown to possess anti-angiogenic activities. This study aims to investigate the effects of THC on adipose angiogenesis and expression of angiogenic factors that occurs in 60% high-fat diet-induced obese mice. Male ICR mice were randomly divided into 3 groups: mice fed with a low-fat diet (LFD group); mice fed with very high fat diet (VHFD group), and mice fed with VHFD supplemented with THC (300 mg/kg/day orally) (VHFD+THC treated group) for 6 weeks. Body weight (BW), food intake, fasting blood sugar (FBS), lipid profiles and visceral fats weight (VF) were measured. The microvascular density (MVD), TNF-α, VEGF, MMP-2, and MMP-9 expressions were evaluated. The VHFD group had significantly increased total cholesterol, triglyceride, food intake, BW, VF, VF/BW ratio, adipocyte size and the number of crown-liked structures as compared to LFD group. THC supplementation markedly reduced these parameters and adipocyte hypertrophy and inflammation in white adipose tissues. MVD, TNF-α, VEGF, MMP-2, and MMP-9 were over-expressed in the VHFD group. However, THC supplementation decreased MVD and reduced expression of TNF-α, VEGF, MMP-2, and MMP-9. In conclusion, THC suppressed angiogenesis in adipose tissue by the downregulation of TNF-α, VEGF, MMP-2, and MMP-9. With its effects on lipid metabolism as well as on food consumption, THC could contribute to lower visceral fat and body weight. Overall, our study demonstrated the potential benefit of THC in mitigating obesity and associated metabolic disorders along with elucidated the suppression of adipose angiogenesis as one of its underlying mechanisms.
ABSTRACT
Background and purpose: Several attempts have been made to synthesize and investigate modified flavonoids to improve their potential anticancer efficacy. This study aimed to determine the in vitro anti-viability, anti-migration, and anti-invasive effects of two novel hesperidin glycosides, hesperidin glucoside (HG1) and hesperidin maltoside (HG2), compared to original hesperidin and diosmin. Experimental approach: Inhibitory effects on normal (MRC5) and cancer (A549) cell viability of hesperidin glycosides were investigated by the trypan blue and MTS assays. A scratch assay determined the suppressive effects on cancer cell migration, and inhibition of cancer cell invasion was investigated through Matrigel™. The selectivity index (SI), a marker of cell toxicity, was also determined for A549 relative to MRC5 cells. Findings/Results: The cell viability trypan blue and MTS assays showed similar results of the inhibition of A549 cancer cells; HG1 and HG2 had lower IC50 than original hesperidin and diosmin. The SI of HG1 and HG2 was > 2 after 72-h culture. Investigation of cell migration showed that HG1 and HG2 inhibited the ability of gap closure in a time- and dose-dependent manner. The infiltration of the Matrigel™-coated filter by A549 cells was suppressed in the presence of HG1 and HG2. This result implied that HG1 and HG2 could inhibit cancer cell invasion. Conclusion and implication: Our results suggest the inhibition of cancer cell migration and invasion in a time- and concentration-related manner with a favorable toxic profile. Moreover, HG1 and HG2 appeared potentially better agents than the original hesperidin for future anticancer development.
ABSTRACT
Introduction: Several parts of Garcinia hanburyi are used in traditional medicine for many purposes. In this study, Garcinia hanburyi resin (GHR) was explored for possible anti-proliferative effects and the underlying mechanism on colorectal cancer (CRC) cells. Methods: Gambogic acid (GA) content in GHR was analyzed by HPLC method. The cytotoxicities of GA and GHR were assessed in human CRC cell lines (SW480 and Caco-2) and normal colon cells (CCD841 CoN) using a trypan blue exclusion assay, MTS assay, and cell morphology analysis. Cell cycle and apoptosis at its half maximal inhibitory concentration (IC50) were analyzed using flow cytometry. And, the levels of intrinsic apoptosis-related proteins were measured by Western blot analysis. Results: GA was the major compound as 71.26% of the GHR. The cell viability of CRC cells was decreased in a time- and dose-dependent manner after exposure to GHR. The selectivity index indicated that GHR had a high degree of selectivity against CRC cells. The same result was obtained for GA treatment. In addition, GHR markedly induced typical apoptotic morphology of CRC cells, but had no obvious effect on normal colon cells. GHR induced apoptosis with the cell cycle arrest at the G2/M phase. An increase in Bax/Bcl-2 ratio and a decrease in procaspase-3 proteins indicated that GHR promoted apoptosis by disrupting the mitochondrial outer membrane permeability and the subsequent activation of caspase-3. Conclusion: GHR, which contained GA as an active compound, significantly inhibited CRC cell proliferation via the induction of intrinsic apoptosis, while having low toxicity on normal colon cells. Therefore, GHR could be proposed as a potent candidate for the treatment of CRC.
ABSTRACT
BACKGROUND: Methyl donor status influences DNA stability and DNA methylation although little is known about effects on DNA methyltransferases. The aim of this study was to determine whether methyldonor status influences DNA methyltransferase (Dnmt) gene expression in cervical cancer cells, and if so, whether there are associated effects on global DNA methylation. MATERIALS AND METHODS: The human cervical cancer cell line, C4 II, was grown in complete medium and medium depleted of folate (FM+) and folate and methionine (FM). Growth rate, intracellular folate, intracellular methionine and homocysteine in the extracellular medium were measured to validate the cancer cell model of methyl donor depletion. Dnmt expression was measured by qRT PCR using relative quantification and global DNA methylation was measured using a flow cytometric method. RESULTS: Intracellular folate and methionine concentrations were significantly reduced after growth in depleted media. Growth rate was also reduced in response to methyl donor depletion. Extracellular homocysteine was raised compared with controls, indicating disturbance to the methyl cycle. Combined folate and methionine depletion led to a significant downregulation of Dnmt3a and Dnmt3b; this was associated with an 18% reduction in global DNA methylation compared with controls. Effects of folate and methionine depletion on Dnmt3a and 3b expression were reversed by transferring depleted cells to complete medium. CONCLUSIONS: Methyl donor status can evidently influence expression of Dnmts in cervical cancer cells, which is associated with DNA global hypomethylation. Effects on Dnmt expression are reversible, suggesting reversible modulating effects of dietary methyl donor intake on gene expression, which may be relevant for cancer progression.
