title: Artocarpus altilis (Parkinson) Fosberg Extracts and Geranyl Dihydrochalcone Inhibit STAT3 Activity in Prostate Cancer DU145 Cells.
abstract: Artocarpus altilis (Parkinson) Fosberg has traditionally been used in Indonesia for the treatment of liver cirrhosis, hypertension, and diabetes. In many other countries, it is used for the treatment of malaria, yellow fever, and dengue fever. It has been reported that A. altilis extracts have antiatherosclerotic and cytoprotective effects, but its molecular targets in tumor cells are not yet fully understood. The A. altilis extracts and the partially purified fraction have been shown to inhibit STAT3 activity and the phosphorylation of STAT3 in a dose-dependent manner. To identify the active components, a bioassay-guided isolation of the partially purified fraction resulted in the identification of a geranyl dihydrochalcone, CG901. Its chemical structure was established on the basis of spectroscopic evidence and comparison with published data. The partially purified fraction and the isolated a geranyl dihydrochalcone, CG901, down-regulated the expression of STAT3 target genes, induced apoptosis in DU145 prostate cancer cells via caspase-3 and PARP degradation, and inhibited tumor growth in human prostate tumor (DU145) xenograft initiation model. These results suggest that A. altilis could be a good natural source and that the isolated compound will be a potential lead molecule for developing novel therapeutics against STAT3-related diseases, including cancer and inflammation.
authors: Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology, 125 Gwahakro Yoosunggu, Daejeon, 305-600, Republic of Korea.
authors: Yoon Jung
authors: YJ
authors: Jeon
authors: Seung-Nam
authors: SN
authors: Jung
authors: Hyeyoun
authors: H
authors: Chang
authors: Jieun
authors: J
authors: Yun
authors: Chang Woo
authors: CW
authors: Lee
authors: Joonku
authors: J
authors: Lee
authors: Sangho
authors: S
authors: Choi
authors: Oyekanmi
authors: O
authors: Nash
authors: Dong Cho
authors: DC
authors: Han
authors: Byoung-Mog
authors: BM
authors: Kwon
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D031622:Artocarpus / Q000737:chemistry*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D047188:Chalcones; D010936:Plant Extracts; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C505407:CASP3 protein, human; D053148:Caspase 3; C015812:dihydrochalcone
keywords: Artocarpus altilis; STAT3; antitumor effects; apoptosis; prostate cancer