Aim:To compare the anti-cancer activity and cellular uptake of curcumin (Cur) delivered by targeted and non-targeted drug delivery systems in multidrug-resistant cervical cancer cells. Methods: Cur was entrapped into poly (DL-lactide-co-glycolide) (PLGA) nanoparticles (Cur-NPs) in the presence of modified-pluronic F127 stabilizer using nano-precipitation technique. On the surface of Cur-NPs, the carboxy-terminal of modified pluronic F127 was conjugated to the amino-terminal of anti-P-glycoprotein (P-gp) (Cur-NPs-APgp). The physical properties of the Cur-NPs, including particle size, zeta potential, particle morphology and Cur release kinetics, were investigated. Cellular uptake and specificity of the Cur-NPs and Cur-NPs-APgp were detected in cervical cancer cell lines KB-V1 (higher expression of P-gp) and KB-3-1 (lower expression of P-gp) using fluorescence microscope and flow cytometry, respectively. Cytotoxicity of the Cur-NPs and Cur-NPs-APgp was determined using MTT assay. Results: The particle size of Cur-NPs and Cur-NPs-APgp was 127 and 132 nm, respectively. The entrapment efficiency and actual loading of Cur-NPs-APgp (60% and 5 µg Cur/mg NP) were lower than those of Cur-NPs (99% and 7 µg Cur/mg NP). The specific binding of Cur-NPs-APgp to KB-V1 cells was significantly higher than that to KB-3-1 cells. Cellular uptake of Cur-NPs-APgp into KB-V1 cells was higher, as compared to KB-3-1 cells. However, the cellular uptake of Cur-NPs and Cur-NPs-IgG did not differ between the two types of cells. Besides, the cytotoxicity of Cur-NPs-APgp in KB-V1 cells was higher than those of Cur and Cur-NPs. Conclusion:The results demonstrate that Cur-NPs-APgp targeted to P-gp on the cell surface membrane of KB-V1 cells, thus enhancing the cellular uptake and cytotoxicity of Cur.

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BACKGROUND/OBJECTIVESSeveral pharmacological properties of red rice extract have been reported including anti-oxidant, anti-tumor, and reduced cancer cell invasion. This study was conducted to evaluate the anti-inflammatory effects of red rice extract on the production of inflammatory mediators in lipopolysaccharide (LPS)-induced Raw 264.7 macrophages.MATERIALS/METHODSPro-inflammatory cytokines including tumor necrosis factor-α and interleukin-6 were determined by ELISA and cyclooxygenase-2 and inducible nitric oxide synthase expression was evaluated using western blot analysis. In addition, the signaling pathway controlling the inflammatory cascade such as nuclear factor kappa B (NF-κB), activator proteins-1 (AP-1), and mitogen-activated protein kinase (MAPK) was determined.RESULTSOur results showed that red rice polar extract fraction (RR-P), but not non-polar extract fraction, inhibited interleukin-6, tumor necrosis factor-α, and nitric oxide production in LPS-induced Raw 264.7 cells. RR-P also reduced the expression of inflammatory enzymes, inducible nitric oxide synthase, and cyclooxygenase-2. In addition, activation of AP-1 and NF-κB transcription factor in the nucleus was abrogated by RR-P. RR-P inhibited the phosphorylation of extracellular signaling-regulated kinase 1/2, c-Jun NH2-terminal kinase, and p38 MAPK signaling responsible for the expression of inflammatory mediators in LPS-stimulated Raw 264.7 cells. Based on chemical analysis, high amounts of proanthocyanidin and catechins were detected in the RR-P fraction. However, only proanthocyanidin reduced NF-κB and AP-1 activation in LPS-activated Raw 264.7 cells.CONCLUSIONThese observations suggest that the anti-inflammatory properties of RR-P may stem from the inhibition of pro-inflammatory mediators via suppression of the AP-1, NF-κB, and MAPKs pathways.

BackgroundNatural products made from plant sources have been used in a variety of cosmetic applications as a source of nutrition and as a whitening agent. The flowers of Cassia fistula L, family Fabaceae, have been used as a traditional medicine for skin diseases and wound healing and have been reported to possess anti-oxidant properties. The anti-aging effect of C. fistula flower extract on human skin fibroblast was investigated.MethodsThe butanolic extraction of C. fistula flowers was completed and the active compounds were classified. The cytotoxicity of fibroblasts was evaluated by SRB assay for the purposes of selecting non-toxic doses for further experiments. The collagen and hyaluronic acid (HA) synthesis was then measured using the collagen kit and ELISA, respectively. Moreover, the enzyme activity, including collagenase, matrixmelloproteinase-2 (MMP-2) and tyrosinase, were also evaluated.ResultsIt was found that the flower extract did not affect skin fibroblast cell growth (IC50 > 200 μg/mL). The results did show that the flower extract significantly increased collagen and HA synthesis in a dose dependent manner. The flower extract (50–200 μg/mL) also significantly inhibited collagenase and MMP-2 activity. Furthermore, this flower extract could inhibit the tyrosinase activity that causes hyperpigmentation, which induces skin aging.ConclusionsThe C. fistula flower extract displayed a preventive effect when used for anti-aging purposes in human skin fibroblasts and may be an appropriate choice for cosmetic products that aim to provide whitening effects, and which are designated as anti-aging facial skin care products.

Recent evidence suggests that oxidative stress contributes to the pathogenesis of prostate cancer. The present study focused on the effect of apocynin, an inhibitor of NADPH oxidase, on prostate carcinogenesis using the transgenic rat for adenocarcinoma of prostate (TRAP) model. There were no toxic effects with apocynin treatment. The percentages and numbers of carcinomas in both the ventral and lateral prostate were significantly reduced by apocynin treatment, with dose dependence. Reduction of reactive oxygen species by apocynin was confirmed by immunohistochemistry of 8-OHdG and dihydroethidium staining. Positivity of Ki67 was significantly reduced by apocynin treatment, and downregulation of clusterin expression, as well as inactivation of the MEK-ERK1 ⁄ 2 pathway, was a feature of the apocynin treated groups. In human prostate cancer cell line LNCaP, apocynin also inhibited reactive oxygen species production and blocked cell growth by inducing G0 ⁄ G1 arrest with downregulation of clusterin and cyclin D1. These data suggest that apocynin possesses chemopreventive potential against prostate cancer. (Cancer Sci 2013; 104: 1711-1717 P rostate cancer is the second most frequently diagnosed cancer in men in the world, with particularly high incidences in Oceania, Europe and North America. In Japan, incident and mortality rates for prostate cancer are relatively low are but increasing.(1,2) There are potentially curative options, such as radical prostatectomy or radiotherapy, but once the disease is metastatic, the outlook is poor. Therefore, research into chemoprevention of prostate cancer is critical.Reactive oxygen species (ROS) can be important factors for carcinogenesis and tumor progression, not only inducing DNA damage but also producing cellular alterations, such as upregulation of MAPK and protein kinase C. (3,4) Recently, oxidative stress has been reported to contribute to cancer and progression in the prostate.(5,6) Therefore, we have focused on inhibition of ROS production as an anti-carcinogenic approach. ROS is produced by mitochondria, peroxisomes, cytochrome P-450 and other cellular elements as a byproduct, and is generated by NADPH oxidase, which is also implicated in a variety of signaling events, including cell growth, cell survival and cell death.(7) Apocynin, which belongs to the methoxysubstituted catechol family, inhibits NADPH oxidase activity by blocking the formation of NADPH oxidase complex (8) and is commonly used as a standard NOX inhibitor for research purposes.(7) In addition, apocynin can be converted by peroxidase-mediated oxidation to a dimer, which has been shown to be a more efficient inhibitor than apocynin itself.(9) We previously presented evidence that apocynin reduced oxidative stress induced by arsenite treatment of rat urothelium in vivo. (10) In the present study we focus on NADPH oxidase and test whether its inhibitor, apocynin, is able to suppress prostate carcinogenesis in the transgenic rat for adenocarcinoma of prostate (TRAP) model, which was generated in our labo...