http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Siveen, K S,Nguyen, A H,Lee, J H,Li, F,Singh, S S,Kumar, A P,Low, G,Jha, S,Tergaonkar, V,Ahn, K S,Sethi, G Nature Publishing Group 2014 The British journal of cancer Vol.111 No.7
<P><B>Background:</B></P><P>Constitutive activation of signal transducer and activator of transcription signalling 3 (STAT3) has been linked with survival, proliferation and angiogenesis in a wide variety of malignancies including hepatocellular carcinoma (HCC).</P><P><B>Methods:</B></P><P>We evaluated the effect of lupeol on STAT3 signalling cascade and its regulated functional responses in HCC cells.</P><P><B>Results:</B></P><P>Lupeol suppressed constitutive activation of STAT3 phosphorylation at tyrosine 705 residue effectively in a dose- and time-dependent manner. The phosphorylation of Janus-activated kinases (JAKs) 1 and 2 and Src was also suppressed by lupeol. Pervanadate treatment reversed the downregulation of phospho-STAT3 induced by lupeol, thereby indicating the involvement of a phosphatase. Indeed, we observed that treatment with lupeol increased the protein and mRNA levels of SHP-2, and silencing of SHP-2 abolished the inhibitory effects of lupeol on STAT3 activation. Treatment with lupeol also downregulated the expression of diverse STAT3-regulated genes and decreased the binding of STAT3 to VEGF promoter. Moreover, the proliferation of various HCC cells was significantly suppressed by lupeol, being associated with substantial induction of apoptosis. Depletion of SHP-2 reversed the observed antiproliferative and pro-apoptotic effects of lupeol.</P><P><B>Conclusions:</B></P><P>Lupeol exhibited its potential anticancer effects in HCC through the downregulation of STAT3-induced pro-survival signalling cascade.</P>
Zhang, J.,Sikka, S.,Siveen, K. S.,Lee, J. H.,Um, J. Y.,Kumar, A. P.,Chinnathambi, A.,Alharbi, S. A.,Rangappa, K. S. Springer Science + Business Media 2017 Apoptosis Vol.22 No.1
<P>The pleiotropic transcription factor, signal transducer and activator of transcription 3 (STAT3) is often aberrantly activated in a wide variety of cancers and plays a pivotal role in tumor initiation, promotion and progression. Targeting deregulated STAT3 activation by small molecule inhibitors is generally considered as an important therapeutic strategy. Hence, in the present study, we evaluated the potential of cardamonin (CD), a 2',4'-dihydroxy-6'-methoxychalcone, to modulate STAT3 activation in prostate cancer (PC) cells and found that this chalcone can indeed exhibit significant anticancer effects through negatively regulating STAT3 activation by diverse molecular mechanism(s). CD suppressed STAT3 phosphorylation, nuclear translocation and DNA binding ability in PC cells. Computational modeling revealed that CD can bind directly to the Src Homology 2 domain of STAT3 and also effectively inhibit its dimerization. CD was also found to significantly reduce the migratory/invasive potential of PC cells through the downregulation of various oncogenic proteins. Overall, the data indicates that the potential application of CD as a STAT3 blocker can mitigate both the growth and survival of PC cells.</P>
Ramachandran, Lalitha,Manu, Kanjoormana Aryan,Shanmugam, Muthu K,Li, Feng,Siveen, Kodappully Sivaraman,Vali, Shireen,Kapoor, Shweta,Abbasi, Taher,Surana, Rohit,Smoot, Duane T,Ashktorab, Hassan,Tan, Pa American Society for Biochemistry and Molecular Bi 2012 The Journal of biological chemistry Vol.287 No.45
<P>Gastric cancer (GC) is a lethal malignancy and the second most common cause of cancer-related deaths. Although treatment options such as chemotherapy, radiotherapy, and surgery have led to a decline in the mortality rate due to GC, chemoresistance remains as one of the major causes for poor prognosis and high recurrence rate. In this study, we investigated the potential effects of isorhamnetin (IH), a 3'-O-methylated metabolite of quercetin on the peroxisome proliferator-activated receptor 관 (PPAR-관) signaling cascade using proteomics technology platform, GC cell lines, and xenograft mice model. We observed that IH exerted a strong antiproliferative effect and increased cytotoxicity in combination with chemotherapeutic drugs. IH also inhibited the migratory/invasive properties of GC cells, which could be reversed in the presence of PPAR-관 inhibitor. We found that IH increased PPAR-관 activity and modulated the expression of PPAR-관 regulated genes in GC cells. Also, the increase in PPAR-관 activity was reversed in the presence of PPAR-관-specific inhibitor and a mutated PPAR-관 dominant negative plasmid, supporting our hypothesis that IH can act as a ligand of PPAR-관. Using molecular docking analysis, we demonstrate that IH formed interactions with seven polar residues and six nonpolar residues within the ligand-binding pocket of PPAR-관 that are reported to be critical for its activity and could competitively bind to PPAR-관. IH significantly increased the expression of PPAR-관 in tumor tissues obtained from xenograft model of GC. Overall, our findings clearly indicate that antitumor effects of IH may be mediated through modulation of the PPAR-관 activation pathway in GC.</P>