title: Cytotoxicity of obacunone and obacunone glucoside in human prostate cancer cells involves Akt-mediated programmed cell death.
abstract: Obacunone and obacunone glucoside (OG) are naturally occurring triterpenoids commonly found in citrus and other plants of the Rutaceae family. The current study reports the mechanism of cytotoxicity of citrus-derived obacunone and OG on human androgen-dependent prostate cancer LNCaP cells. Both limonoids exhibited time- and dose-dependent inhibition of cell proliferation, with more than 60% inhibition of cell viability at 100 μM, after 24 and 48 h. Analysis of fragmentation of DNA, activity of caspase-3, and cytosolic cytochrome-c in the cells treated with limonoids provided evidence for activation of programmed cell death by limonoids. Treatment of LNCaP cells with obacunone and OG resulted in dose-dependent changes in expression of proteins responsible for the induction of programmed cell death through the intrinsic pathway and down-regulation of Akt, a key molecule in cell signaling pathways. In addition, obacunone and OG also negatively regulated an inflammation-associated transcription factor, androgen receptor, and prostate-specific antigen, and activated proteins related to the cell cycle, confirming the ability of limonoids to induce cytotoxicity through multiple pathways. The results of this study provided, for the first time, an evidence of the cytotoxicity of obacunone and OG in androgen-dependent human prostate cancer cells.
authors.affiliation: Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, TX 77845-2119, United States.
authors.forename: Kotamballi N Chidambara
authors.initials: KN
authors.lastname: Murthy
authors.affiliation: Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, TX 77845-2119, United States. Electronic address: gkjp@tamu.edu.
authors.forename: Guddadarangavvanahally K
authors.initials: GK
authors.lastname: Jayaprakasha
authors.affiliation: Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, TX 77845-2119, United States. Electronic address: b-patil@tamu.edu.
authors.forename: Bhimanagouda S
authors.initials: BS
authors.lastname: Patil
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001584:Benzoxepins / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D032083:Citrus paradisi / Q000737:chemistry; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D036701:Limonins / Q000494:pharmacology*; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: C410798:AR protein, human; D001584:Benzoxepins; D005960:Glucosides; D036701:Limonins; D010936:Plant Extracts; D011944:Receptors, Androgen; D014315:Triterpenes; C411188:obacunone glucoside; C067207:obacunone; D045304:Cytochromes c; D051057:Proto-Oncogene Proteins c-akt; D017430:Prostate-Specific Antigen; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Cell signal; Citrus; Inflammation; LNCaP cells; Limonoids; Programmed cell death; Prostate-specific antigen