title: Garcinol inhibits cell proliferation and promotes apoptosis in pancreatic adenocarcinoma cells.
abstract: Garcinol, or polyisoprenylated benzophenone, isolated from the rind of fruiting bodies of Garcinia indica, has been used in traditional medicine for its potential antiinflammatory and antioxidant properties. The objective of this study was to investigate the effect of garcinol on pancreatic cancer (PaCa) cell viability and proliferation. For this, 2 human PaCa cell lines, BxPC-3 and Panc-1, with wild and mutant k-ras, respectively, were treated with garcinol (0-40 μM). Garcinol significantly (P < 0.05) inhibited cell growth (trypan blue exclusion) by induction of apoptosis in a dose- and time-dependent manner. Flow cytometric analysis revealed G0-G1 phase cell cycle arrest in both cell lines. The molecular mechanism of garcinol's action on PaCa cells was investigated by targeting signaling moieties involved in apoptosis (X-IAP, cIAP, caspase-3, 9, and PARP cleavage), transcription factor NF-κB, believed to contribute toward a chemoresistance phenotype in pancreatic tumors, and molecules associated with neovascularization and metastasis (MMP-9, VEGF, IL-8, and PGE(2)). Garcinol significantly (P < 0.05) augmented antiproliferative, proapoptotic, antimetastatic, and antiangiogenic effects in both PaCa cell types relative to untreated cells. These effects were more pronounced in Panc-1. This is the first report on the therapeutically relevant effect of garcinol in PaCa. Further studies are warranted, based on our findings.
authors.affiliation: Department of Nutrition and Food Science, Wayne State University, Detroit, Michigan, USA.
authors.forename: Mansi A
authors.initials: MA
authors.lastname: Parasramka
authors.forename: Smiti V
authors.initials: SV
authors.lastname: Gupta
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D015232:Dinoprostone / Q000378:metabolism; D011905:Genes, ras; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D015398:Signal Transduction; D013729:Terpenes / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D016328:NF-kappa B; D013729:Terpenes; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone; C054597:garcinol