Induction of cytochrome p450 isozymes is the major cause for clinical drug interactions of St. John's wort. The relationships of St. John's wort to cytochrome p450 isoforms have been fully investigated, but its effect on CYP2C19 is lacking. Thus, the aim of the present study was to observe the effect of St. John's wort on CYP2C19 activity using CYP1A2 as a control. Twelve healthy adult men-6 extensive metabolizers of CYP2C19 (2C19(*)1/2C19(*)1) and 6 poor metabolizers (4 2C19(*)2/2C19(*)2 and 2 2C19(*)2/2C19(*)3)-were enrolled in a two-phase, randomized, crossover manner. All subjects took a 300-mg St. John's wort tablet or placebo three times daily for 14 days, and then the activities of CYP2C19 and CYP1A2 were measured using mephenytoin and caffeine. It was found that St. John's wort treatment significantly increased CYP2C19 activity in CYP2C19 wild-genotype subjects, with urinary 4'-hydroxymephenytoin excretion raised by 151.5% +/- 91.9% (p = 0.0156), whereas no significant alteration was observed for CYP2C19 poor metabolizers. Repeated St. John's wort administration did not affect the CYP1A2 phenotypic ratio for both CYP2C19 genotype subjects. In conclusion, St. John's wort is an inducer to the human CYP2C19, and clinicians should pay great attention when St. John's wort is added to or withdrawn from an existing drug regimen containing substrates for such enzymes.

Abstract. Curcumin is a non-nutritive yellow pigment found in the spice turmeric, which is derived from the rhizome of the plant Curcuma longa Linn. Six cyclohexanone analogues of curcumin (A 1 -A 6 ) were investigated for their effects on growth and apoptosis in PC-3 human prostate cancer cells. The ability of these compounds to inhibit NF-κB activity in PC-3 cells was also determined. Five out of the six curcumin analogues (A 2 -A 6 ) had stronger inhibitory effects compared to curcumin on the growth of cultured PC-3 cells. Compounds A 2 -A 6 also had stronger stimulatory effects on apoptosis in PC-3 cells than curcumin, and these curcumin analogues more potently inhibited NF-κB activity than curcumin. The inhibitory effects of these compounds on NF-κB activity correlated with their effects on growth inhibition and apoptosis stimulation in PC-3 cells. The results of the present study provide a rationale for in vivo studies with A 2 -A 6 using suitable animal models of prostate cancer. IntroductionCurcumin is a non-nutritive yellow pigment found in the spice turmeric, which is derived from the rhizome of the plant Curcuma longa Linn. Curcumin lacks toxicity in humans (1), and extensive research over several decades has revealed that curcumin possesses anticancer, anti-inflammatory, antioxidant, antiviral and anti-bacterial activities (2,3). Curcumin suppressed cell proliferation or induced apoptosis in cultured prostate cancer cells and other types of cancer cells (4-10). Curcumin also inhibited prostate carcinogenesis (11). Studies from our laboratory and those of other authors have demonstrated enhanced anticancer activities of curcumin when combined with other anticancer agents (12-14). Findings of earlier studies showed that curcumin exerts a wide range of anticancer effects by modulating a diversity of signaling pathways, including nuclear factor-κB (NF-κB) and other pathways (15)(16)(17)(18)(19)(20). Curcumin has entered clinical trials for certain types of human cancer (21-23). However, the clinical efficacy of curcumin is limited, which is likely to be due to its low bioavailability (21-23). It was suggested that the β-diketone moiety of curcumin causes instability and poor metabolic properties (24-26). Enhanced stability was found in curcumin analogues by deleting the β-diketone moiety of the molecule (27). Recently, it was demonstrated that the cyclohexanone analogues of curcumin have enhanced stability in biological medium compared to curcumin (28). The cyclohexanone-containing curcumin analogue 2,6-bisp[(3-methoxy-4-hydroxyphenyl)methylene)]-cyclohexanone was found to be more potent than curcumin for inhibiting NF-κB in human breast cancer cells in vitro (29).In an earlier study, we synthesized a series of cyclohexanone curcumin analogues and determined their inhibitory effect on the activity of aldose reductase (30). In the present study, we investigated the effects of these curcumin analogues on the growth and apoptosis of human prostate cancer PC-3 cells. We also determined the inhibitory effect ...

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The 5‐year survival rate of patients with glioma is < 5%, and therefore there is an urgent need to find novel potential targets for facilitating its diagnosis and treatment. The long non‐coding RNA (lnc RNA ) UCA 1 has been shown to promote the proliferation and invasion of cervical cancer cells through regulating miR‐206 expression, but the involvement of UCA 1 in regulating the stemness and epithelial–mesenchymal transition ( EMT ) of glioma cells is unknown. Here, we report that the expression of UCA 1 is significantly increased by transforming growth factor‐β ( TGF ‐β) treatment in glioma cells and is greater in glioma tissues than in normal adjacent tissues. Additionally, TGF ‐β induced EMT and the stemness of glioma cells, whereas knockdown of lnc RNA UCA 1 attenuated these two processes and their enhancement by TGF ‐β. Mechanistically, knockdown of UCA 1 decreased Slug expression by acting as a competitive endogenous RNA (ce RNA ) through competitive binding with miR‐1 and miR‐203a; this effect was further evidenced by the fact that transfection with miR‐1 or miR‐203a inhibitors abrogated the effects of UCA 1 knockdown on Slug expression, and UCA 1 colocalized with miR‐1 and miR‐203a in glioma tissues. Notably, ectopic expression of Slug rescued the attenuation of UCA 1 knockdown on EMT and the stemness of glioma cells. These results indicate that UCA 1 may act as a ce RNA to promote Slug expression, which underlies TGF ‐β‐induced EMT and stemness of glioma cells.