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

College of Oriental Medicine and Institute of Oriental Medicine, Kyung Hee University, 1 Hoegidong Dongdaemungu, Seoul, 130-701, Korea.
Phytotherapy Research (Impact Factor: 2.66). 01/2013; 27(1). DOI: 10.1002/ptr.4689
Source: PubMed


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.

1 Follower
23 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The treatment landscape for patients with castration-resistant prostate cancer (CRPC) is undergoing significant changes with the advent of new therapies and multidisciplinary efforts by scientists and clinicians. As activation of multiple molecular pathways in the neoplastic prostate makes it impossible for single-target drugs to be completely effective in treating CRPC, this has led to combination therapy strategy, where several molecules involved in tumor growth and disease progression are targeted by a therapeutic regimen. In the present review, we provide an update on the molecular pathways that play an important role in the pathogenesis of CRPC and discuss the current wave of new treatments to combat this lethal disease.
    Full-text · Article · Aug 2012 · Biologics: Targets & Therapy
  • [Show abstract] [Hide abstract]
    ABSTRACT: Liver cancers remain one main reason for the mortality in patients with tumors. Up to now, however, the effective drugs to treat liver cancers are limited. The aim of this study was to study whether Scutellarin which was widely found in many medicinal plants can exert an inhibitory role in HepG2 hepatocellular carcinoma cell lines, and to explore its molecular mechanisms. The MTT assay showed that Scutellarin markedly inhibited the proliferation of HepG2 cells in a concentration- and time-dependent manner. Moreover, Scutellarin-treated cells exhibited typical apoptotic appearance by staining assay. Also, Scutellarin-treated HepG2 cells exhibited the reduction of ROS production, compared with untreated HepG2 cells. Western blot analysis displayed that STAT3 protein was obviously decreased in Scutellarin-treated HepG2 cells. Furthermore, STAT3 transcriptional targets Bcl-XL and Mcl-1 were also downregulated in HepG2 cells treated by Scutellarin. In summary, we found that Scutellarin was able to inhibit the proliferation and induce the apoptosis of HepG2 cells via a STAT3 signal pathway, which provided evident support for developing Scutellarin as an alternative treatment for liver cancer. Copyright © 2012 John Wiley & Sons, Ltd.
    No preview · Article · Nov 2012 · Phytotherapy Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: The flower of the chrysanthemum plant Shiranui Himekiku has been used as a folk medicine for a variety of diseases including cancer, and cytotoxic effects in some cancer lines have been reported. However, little is known about the anti-cancer activity of the leaf extract and its active compounds. Therefore, to clarify the anti-cancer activity of Shiranui Himekiku leaf and flower, the anti-proliferative effects of the extracts on human cancer cells were examined. Both leaf and flower water extracts dose-dependently suppressed the proliferation of the human breast cancer cell line MCF-7 at concentrations > 25 μg/ml. Furthermore, the anti-proliferative effect in MCF-7 is more than four times that in normal human dermal fibroblast cells. When heated at 100°C for 30 minutes, the proliferation inhibitory activity of the flower extract was unchanged. In contrast, under identical conditions, the activity of the leaf extract was lost. The extracts were separated into two fractions ; one with a molecular weight (MW) > 10 000 (high molecular weight fraction) (HMW) and the other with a MW < 10 000 (low molecular weight fraction) (LMW). A significant proliferation inhibitory effect can be seen in the LMW fraction of both extracts, but the HMW fraction of the leaf extract also slightly inhibits cell growth. Both polyphenols and non-polyphenols are candidate active compounds because the anti-cancer effect was seen in the polyphenol- and non-polyphenol-fractions. These results suggest that the extracts contain several types of anti-cancer components and that both leaves and flowers can be useful.
    No preview · Article · Jan 2013 · Nippon Shokuhin Kagaku Kogaku Kaishi
Show more