Arctigenin Anti-Tumor Activity in Bladder Cancer T24 Cell Line Through Induction of Cell-Cycle Arrest and Apoptosis

Department of Anatomy, Harbin Medical University, Harbin, China.
The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology (Impact Factor: 1.54). 08/2012; 295(8):1260-6. DOI: 10.1002/ar.22497
Source: PubMed


Bladder cancer is the most common neoplasm in the urinary system. This study assesses arctigenin anti-tumor activity in human bladder cancer T24 cells in vitro and the underlying molecular events. The flow cytometry analysis was used to detect cell-cycle distribution and apoptosis. Western blotting was used to detect changes in protein expression. The data showed that arctigenin treatment reduced viability of bladder cancer T24 cells in a dose- and time-dependent manner after treatment with arctigenin (10, 20, 40, 80, and 100 μmol/L) for 24 hr and 48 hr. Arctigenin treatment clearly arrested tumor cells in the G1 phase of the cell cycle. Apoptosis was detected by hoechst stain and flow cytometry after Annexin-V-FITC/PI double staining. Early and late apoptotic cells were accounted for 2.32-7.01% and 3.07-7.35%, respectively. At the molecular level, arctigenin treatment decreased cyclin D1 expression, whereas CDK4 and CDK6 expression levels were unaffected. Moreover, arctigenin selectively altered the phosphorylation of members of the MAPK superfamily, decreasing phosphorylation of ERK1/2 and activated phosphorylation of p38 significantly in a dose-dependent manner. These results suggest that arctigenin may inhibit cell viability and induce apoptosis by direct activation of the mitochondrial pathway, and the mitogen-activated protein kinase pathway may play an important role in the anti-tumor effect of arctigenin. The data from the current study demonstrate the usefulness of arctigenin in bladder cancer T24 cells, which should further be evaluated in vivo before translation into clinical trials for the chemoprevention of bladder cancer.

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    • "Arctiin and ATG (Figure 2(a)), the main compounds of AL, have been reported to contain a variety of biological activities [36]. Among those compounds, we selected ATG because it has been shown to have beneficial biopharmaceutical properties and activities in the treatment of many diseases [37, 38]. "
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    ABSTRACT: To identify the active compound arctigenin in Fructus Arctii (dried seed of medicinal plant Arctium lappa) and to elucidate the inhibitory mechanism in melanogenesis, we analyzed melanin content and tyrosinase activity on B16BL6 murine melanoma and melan-A cell cultures. Water extracts of Fructus Arctii were shown to inhibit tyrosinase activity in vitro and melanin content in α -melanocyte stimulating hormone-stimulated cells to similar levels as the well-known kojic acid and arbutin, respectively. The active compound arctigenin of Fructus Arctii displayed little or no cytotoxicity at all concentrations examined and decreased the relative melanin content and tyrosinase activity in a dose-dependent manner. Melanogenic inhibitory activity was also identified in vivo with zebrafish embryo. To determine the mechanism of inhibition, the effects of arctigenin on tyrosinase gene expression and tyrosinase promoter activity were examined. Also in addition, in the signaling cascade, arctigenin dose dependently decreased the cAMP level and promoted the phosphorylation of extracellular signal-regulated kinase. This result suggests that arctigenin downregulates cAMP and the tyrosinase enzyme through its gene promoter and subsequently upregulates extracellular signal-regulated kinase activity by increasing phosphorylation in the melanogenesis signaling pathway, which leads to a lower melanin content.
    Evidence-based Complementary and Alternative Medicine 05/2013; 2013(10):965312. DOI:10.1155/2013/965312 · 1.88 Impact Factor
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    • "V experimentu na T24 buňkách karcinomu močového měchýře zastavoval arctigenin buněčný cyklus v G1 fázi a vyvolával apoptózu nádorových buněk. Zaznamenáno bylo snížení hladiny cyklinu D1 (Yang et al., 2012). Arctigenin způsobuje také apoptózu MH60 leukemických buněk (Matsumoto et al., 2006). "

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