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.

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Cancer metastasis is a major cause of death in cancer patients, with invasion as a first step greatly contributing to the failure of clinical treatments. Any compounds with an inhibitory influence on this process are therefore of prime interest. Momordica charantia (bitter melon) is widely consumed as a vegetable and especially as a folk medicine in Asia. Here, we investigated the anti-invasive effects of bitter melon leaf extract (BMLE) on a rat prostate cancer cell line (PLS10) in vitro and in vivo. The results indicated that nontoxic concentrations of BMLE significantly inhibited the migration and invasion of cells in vitro. The results of zymography showed that BMLE inhibited the secretion of MMP-2, MMP-9 and urokinase plasminogen activator (uPA) from PLS10. Real-time RT-PCR revealed that BMLE not only significantly decreased gene expression of MMP-2 and MMP-9, but also markedly increased the mRNA level of TIMP-2, known to have inhibitory effects on the activity of MMP-2. An EnzChek gelatinase/collagenase assay showed that collagenase type IV activity was partially inhibited by BMLE. In the in vivo study, intravenous inoculation of PLS10 to nude mice resulted in a 100% survival rate in the mice given a BMLE-diet as compared with 80% in the controls. The incidence of lung metastasis did not show any difference, but the percentage lung area occupied by metastatic lesions was slightly decreased in the 0.1% BMLE treatment group and significantly decreased with 1% BMLE treatment as compared with the control. Thus, the results indicate for the first time an anti-metastatic effect of BMLE both in vitro and in vivo. (Cancer Sci 2010; 101: 2234-2240 P rostate cancer is the most common male malignant tumor in Western countries.(1) Androgen ablation therapy is widely used for the initial stage of this disease and may produce favorable outcome, but most patients eventually develop ablationresistant prostate cancers with metastatic foci. Currently, there is no treatment that is able to cure progressive hormone-refractory metastatic prostate cancer.Metastasis is a multi-step process, which involves a series of processes including cellular adhesion and invasion through the basement membrane, transfer via the circulation system, extravasation, and proliferation at a distant site.(2,3) Multiple organ failure caused by multiple metastasis is a major cause of death in cancer patients. Therefore, prevention of tumor metastasis is one primary goal. However, cytotoxic agents have generally been applied for tumor metastasis therapy, with serious sideeffects that can diminish the quality of life of cancer patients. Recently, many efforts have therefore been made to search for non-or low-cytotoxic agents that can reduce the spread of malignant tumors. One focus is on cell invasion using substances in medicinal plants. (5,6) Momordica charantia, or bitter melon, has long been frequently used in various Asian traditional medicine systems and commonly consumed as a vegetable. (7,8) (19) Our previous study showed that the bitter melon ...