Chrysanthemum indicum L. Extract Induces Apoptosis through Suppression of Constitutive STAT3 Activation in Human Prostate Cancer DU145 Cells

Authors
Kim, ChulwonKim, Moo-ChangKim, Sung-MooNam, DongwooChoi, Seung-HoonKim, Sung-HoonAhn, Kyoo SeokLee, Eun HaJung, Sang HoonAhn, Kwang Seok
Issue Date
2013-01
Publisher
WILEY-BLACKWELL
Citation
PHYTOTHERAPY RESEARCH, v.27, no.1, pp.30 - 38
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, CH2Cl2, 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 (C) 2012 John Wiley & Sons, Ltd.
Keywords
NF-KAPPA-B; HEPATOCELLULAR-CARCINOMA; SIGNAL TRANSDUCERS; MYELOMA CELLS; INDUCTION; PHOSPHORYLATION; TRANSCRIPTION; INFLAMMATION; INHIBITION; RESISTANCE; NF-KAPPA-B; HEPATOCELLULAR-CARCINOMA; SIGNAL TRANSDUCERS; MYELOMA CELLS; INDUCTION; PHOSPHORYLATION; TRANSCRIPTION; INFLAMMATION; INHIBITION; RESISTANCE; Chrysanthemum indicum L; STAT3; apoptosis; DU145
ISSN
0951-418X
URI
https://pubs.kist.re.kr/handle/201004/128495
DOI
10.1002/ptr.4689
Appears in Collections:
KIST Article > 2013
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