title: Crocus sativus stigma extract and its major constituent crocin possess significant antiproliferative properties against human prostate cancer.
abstract: In this study, we investigated the antiproliferative effects of saffron extract (SE) and its major constituent crocin on 5 different malignant and 2 nonmalignant prostate cancer cell lines. Using high performance liquid chromatography (HPLC), the purity and content of crocin were determined. All cells were incubated with different concentrations of SE or crocin for 48 h. Cell cycle and apoptosis were also evaluated. In a time- and concentration-dependent manner, both SE and crocin reduced cell proliferation in all malignant cell lines with IC50 values ranging between 0.4 and 4 mg/ml for SE and between 0.26 and 0.95 mM/ml for crocin. Nonmalignant cells were not affected. Flow cytometry profiles revealed that most cells were arrested at G0/G1 phase with a significant presence of apoptotic cells. Western blot analysis revealed that the expression of Bcl-2 was strikingly downregulated, whereas Bax was upregulated. Analysis of caspase activity indicated a caspase-dependent pathway with involvement of caspase-9 activation, suggesting an intrinsic pathway. Based on these findings, it can be concluded that both SE and crocin can inhibit cell proliferation, arrest cell cycle progression, inducing apoptosis in prostate cancer. Consequently, these agents could potentially be used as a chemopreventive as well as a chemotherapeutic agent for prostate cancer management.
authors.affiliation: Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy. dalessandro@cc.univaq.it
authors.forename: Anna M
authors.initials: AM
authors.lastname: D'Alessandro
authors.forename: Andrea
authors.initials: A
authors.lastname: Mancini
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Lizzi
authors.forename: Angela
authors.initials: A
authors.lastname: De Simone
authors.forename: Carmine Esposito
authors.initials: CE
authors.lastname: Marroccella
authors.forename: Giovanni Luca
authors.initials: GL
authors.lastname: Gravina
authors.forename: Carla
authors.initials: C
authors.lastname: Tatone
authors.forename: Claudio
authors.initials: C
authors.lastname: Festuccia
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002338:Carotenoids / Q000494:pharmacology*; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D027622:Crocus / Q000737:chemistry*; D015536:Down-Regulation; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D010936:Plant Extracts; D051028:bcl-2-Associated X Protein; D002338:Carotenoids; C029036:crocin; C506433:CASP9 protein, human; D053453:Caspase 9