title: Cardamonin represses proliferation, invasion, and causes apoptosis through the modulation of signal transducer and activator of transcription 3 pathway in prostate cancer.
abstract: 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.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore.|Cancer Science Institute of Singapore, Centre for Translational Medicine, 14 Medical Drive, #11-01M, Singapore, 117599, Singapore.
authors.forename: Sakshi
authors.initials: S
authors.lastname: Sikka
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore.
authors.forename: Kodappully S
authors.initials: KS
authors.lastname: Siveen
authors.affiliation: Department of Korean Pathology, College of Korean Medicine, Kyung Hee University, #47, Kyungheedae-gil, 1 Hoegi-Dong Dongdaemun-Gu, Seoul, 130-701, Republic of Korea.
authors.forename: Jong Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Korean Pathology, College of Korean Medicine, Kyung Hee University, #47, Kyungheedae-gil, 1 Hoegi-Dong Dongdaemun-Gu, Seoul, 130-701, Republic of Korea.
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Um
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore.|Cancer Science Institute of Singapore, Centre for Translational Medicine, 14 Medical Drive, #11-01M, Singapore, 117599, Singapore.|School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Perth, WA, 6009, Australia.|Department of Biological Sciences, University of North Texas, Denton, TX, 76203, USA.
authors.forename: Alan Prem
authors.initials: AP
authors.lastname: Kumar
authors.affiliation: Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.
authors.forename: Arunachalam
authors.initials: A
authors.lastname: Chinnathambi
authors.affiliation: Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.
authors.forename: Sulaiman Ali
authors.initials: SA
authors.lastname: Alharbi
authors.affiliation: Laboratory of Chemical Biology, Department of Chemistry, Bangalore University, Central College Campus, Palace Road, Bangalore, 560001, India.
authors.lastname: Basappa
authors.affiliation: Department of Studies in Chemistry, Manasagangotri, University of Mysore, Mysore, 570006, India.
authors.forename: Kanchugarakoppal S
authors.initials: KS
authors.lastname: Rangappa
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore.|School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Perth, WA, 6009, Australia.
authors.forename: Gautam
authors.initials: G
authors.lastname: Sethi
authors.affiliation: Department of Korean Pathology, College of Korean Medicine, Kyung Hee University, #47, Kyungheedae-gil, 1 Hoegi-Dong Dongdaemun-Gu, Seoul, 130-701, Republic of Korea. ksahn@khu.ac.kr.
authors.forename: Kwang Seok
authors.initials: KS
authors.lastname: Ahn
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000008:administration & dosage*; D019281:Dimerization; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000235:genetics; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D047188:Chalcones; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C436747:cardamonin
keywords: Cardamonin; Prostate cancer; SH2 domain; STAT3