title: 6-Shogaol from dried ginger inhibits growth of prostate cancer cells both in vitro and in vivo through inhibition of STAT3 and NF-κB signaling.
abstract: Despite much recent progress, prostate cancer continues to represent a major cause of cancer-related mortality and morbidity in men. Prostate cancer is the most common nonskin neoplasm and second leading cause of death in men. 6-Shogaol (6-SHO), a potent bioactive compound in ginger (Zingiber officinale Roscoe), has been shown to possess anti-inflammatory and anticancer activity. In the present study, the effect of 6-SHO on the growth of prostate cancer cells was investigated. 6-SHO effectively reduced survival and induced apoptosis of cultured human (LNCaP, DU145, and PC3) and mouse (HMVP2) prostate cancer cells. Mechanistic studies revealed that 6-SHO reduced constitutive and interleukin (IL)-6-induced STAT3 activation and inhibited both constitutive and TNF-α-induced NF-κB activity in these cells. In addition, 6-SHO decreased the level of several STAT3 and NF-κB-regulated target genes at the protein level, including cyclin D1, survivin, and cMyc and modulated mRNA levels of chemokine, cytokine, cell cycle, and apoptosis regulatory genes (IL-7, CCL5, BAX, BCL2, p21, and p27). 6-SHO was more effective than two other compounds found in ginger, 6-gingerol, and 6-paradol at reducing survival of prostate cancer cells and reducing STAT3 and NF-κB signaling. 6-SHO also showed significant tumor growth inhibitory activity in an allograft model using HMVP2 cells. Overall, the current results suggest that 6-SHO may have potential as a chemopreventive and/or therapeutic agent for prostate cancer and that further study of this compound is warranted.
authors.affiliation: Authors' Affiliations: Division of Pharmacology and Toxicology and Department of Nutritional Sciences, Dell Pediatric Research Institute; and Department of Chemistry, The University of Texas at Austin, Austin, Texas.
authors.forename: Achinto
authors.initials: A
authors.lastname: Saha
authors.affiliation: Authors' Affiliations: Division of Pharmacology and Toxicology and Department of Nutritional Sciences, Dell Pediatric Research Institute; and Department of Chemistry, The University of Texas at Austin, Austin, Texas.
authors.forename: Jorge
authors.initials: J
authors.lastname: Blando
authors.affiliation: Authors' Affiliations: Division of Pharmacology and Toxicology and Department of Nutritional Sciences, Dell Pediatric Research Institute; and Department of Chemistry, The University of Texas at Austin, Austin, Texas.
authors.forename: Eric
authors.initials: E
authors.lastname: Silver
authors.affiliation: Authors' Affiliations: Division of Pharmacology and Toxicology and Department of Nutritional Sciences, Dell Pediatric Research Institute; and Department of Chemistry, The University of Texas at Austin, Austin, Texas.
authors.forename: Linda
authors.initials: L
authors.lastname: Beltran
authors.affiliation: Authors' Affiliations: Division of Pharmacology and Toxicology and Department of Nutritional Sciences, Dell Pediatric Research Institute; and Department of Chemistry, The University of Texas at Austin, Austin, Texas.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sessler
authors.affiliation: Authors' Affiliations: Division of Pharmacology and Toxicology and Department of Nutritional Sciences, Dell Pediatric Research Institute; and Department of Chemistry, The University of Texas at Austin, Austin, TexasAuthors' Affiliations: Division of Pharmacology and Toxicology and Department of Nutritional Sciences, Dell Pediatric Research Institute; and Department of Chemistry, The University of Texas at Austin, Austin, Texas john.digiovanni@austin.utexas.edu.
authors.forename: John
authors.initials: J
authors.lastname: DiGiovanni
mesh_terms: D000818:Animals; D002396:Catechols / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D057141:Food, Preserved; D020939:Zingiber officinale / Q000737:chemistry; D006801:Humans; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010936:Plant Extracts / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002396:Catechols; D016328:NF-kappa B; D010936:Plant Extracts; D050796:STAT3 Transcription Factor; C040115:shogaol