Chrysanthemum indicum L. Extract Induces Apoptosis through Suppression of Constitutive STAT3 Activation in Human Prostate Cancer DU145 Cells
ABSTRACT Chrysanthemum indicum L. has been shown to possess antiinflammatory and anticancer activities, but its molecular targets/pathways are not yet fully understood in tumor cells. In the present study, the potential effects of C. indicum on signal transducer and activator of transcription 3 (STAT3) signaling pathway in different tumor cells were examined. The solvent fractions (hexane, CH(2) Cl(2) , EtOAc, and BuOH,) were obtained from a crude extract (80% EOH extract) of C. indicum. The methylene chloride fraction of C. indicum (MCI) exhibited strong cytotoxic activity as compared with the other fractions and clearly suppressed constitutive STAT3 activation against both DU145 and U266 cells, but not MDA-MB-231 cells. The suppression of constitutive STAT3 activation by MCI is associated with blocking upstream JAK1 and JAK2, but not Src. MCI downregulated the expression of STAT3-regulated gene products; this is correlated with the accumulation of the cell cycle at sub-G1 phase, the induction of caspase-3 activation, and apoptosis. Moreover, the major components of the MCI were bioactive compounds such as sudachitin, hesperetin, chrysoeriol, and acacetin. Sudachitin, chrysoeriol, and acacetin also exerted significantly cytotoxicity, clearly suppressed constitutive STAT3 activation, and induced apoptosis, although hesperetin did not show any significant effect in DU145 cells. Overall, our results demonstrate that MCI could induce apoptosis through inhibition of the JAK1/2 and STAT3 signaling pathways. Copyright © 2012 John Wiley & Sons, Ltd.
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ABSTRACT: The risk of bone-related diseases increases due to the imbalance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively. The goal in the development of antiosteoporotic treatments is an agent that will improve bone through simultaneous osteoblast stimulation and osteoclast inhibition without undesirable side effects. To achieve this goal, numerous studies have been performed to identify novel approaches using natural oriental herbs to treat bone metabolic diseases. In the present study, we investigated the effect of Chrysanthemum indicum extract (CIE) on the differentiation of osteoclastic and osteoblastic cells. CIE inhibited the formation of TRAP-positive mature osteoclasts and of filamentous-actin rings and disrupted the bone-resorbing activity of mature osteoclasts in a dose-dependent manner. CIE strongly inhibited Akt, GSK3β, and IκB phosphorylation in RANKL-stimulated bone marrow macrophages and did not show any effects on MAP kinases, including p38, ERK, and JNK. Interestingly, CIE also enhanced primary osteoblast differentiation via upregulation of the expression of alkaline phosphatase and the level of extracellular calcium concentrations during the early and terminal stages of differentiation, respectively. Our results revealed that CIE could have a potential therapeutic role in bone-related disorders through its dual effects on osteoclast and osteoblast differentiation.Evidence-based Complementary and Alternative Medicine 01/2014; 2014:176049. DOI:10.1155/2014/176049 · 2.18 Impact Factor
Dataset: PLR 56 67 2014
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ABSTRACT: Citrus fruits are important health promoting fruits rich in a number of bioactive components mainly flavonoids, limonoids, coumarins, volatile oils and carotenoids. Citrus bioactives have been found to scavenge reactive oxygen species, rejuvenate body's own antioxidant enzymes, inhibit various signalling pathways, act on extrinsic and intrinsic apoptotic pathways, suppress inflammatory mediators and arrest the cell cycle. Cancer is the second leading cause of death worldwide after cardiovascular diseases and colon cancer is the third most common cancer worldwide. Studies have suggested a positive relation between diet rich in natural phytochemicals and reduced risk of colon cancer. The present review highlights the chemopreventive action of various citrus phytochemicals in colon cancer. The studies suggest that citrus bioactives either alone or in combination with current therapeutic agents can be developed as potential drug candidates for colon cancer.