title: Fermented Brown Rice Extract Causes Apoptotic Death of Human Acute Lymphoblastic Leukemia Cells via Death Receptor Pathway.
abstract: Mixture of brown rice and rice bran fermented with Aspergillus oryzae, designated as FBRA, has been reported to reveal anti-carcinogenic and anti-inflammatory effects in rodents. Then, to test its potential anti-cancer activity, the aqueous extract was prepared from FBRA powder, and the effect of this extract on human acute lymphoblastic leukemia Jurkat cells was directly examined. The exposure to FBRA extract reduced the cell viability in a concentration- and time-dependent manner. The reduction of the cell viability was accompanied by the DNA fragmentation, and partially restored by treatment with pan-caspase inhibitor. Further studies showed that FBRA extract induced the cleavage of caspase-8, -9, and -3, and decreased Bcl-2 protein expression. Moreover, the expression of tBid, DR5, and Fas proteins was enhanced by FBRA extract, and the pretreatment with caspase-8 inhibitor, but not caspase-9 inhibitor, restored the reduction of the cell viability induced by FBRA extract. These findings suggested that FBRA extract could induce the apoptotic death of human acute lymphoblastic leukemia cells probably through mainly the death receptor-mediated pathway and supplementarily through the tBid-mediated mitochondrial pathway, proposing the possibility that FBRA was a potential functional food beneficial to patients with hematological cancer.
authors.affiliation: Research and Development Division, Koken Co., Ltd., 329, Nakagoya, Tobetsu, Ishikari-gun, Hokkaido, 061-0211, Japan. horie@genmaikoso.co.jp.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Horie
authors.affiliation: Research and Development Division, Koken Co., Ltd., 329, Nakagoya, Tobetsu, Ishikari-gun, Hokkaido, 061-0211, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Nemoto
authors.affiliation: Research and Development Division, Koken Co., Ltd., 329, Nakagoya, Tobetsu, Ishikari-gun, Hokkaido, 061-0211, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Itoh
authors.affiliation: Research and Development Division, Koken Co., Ltd., 329, Nakagoya, Tobetsu, Ishikari-gun, Hokkaido, 061-0211, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kosaka
authors.affiliation: Life Science Research Group, Shikoku University School of Health Sciences, Ohjin, Tokushima, 771-1192, Japan.
authors.forename: Kyoji
authors.initials: K
authors.lastname: Morita
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8 / Q000096:biosynthesis; D061945:Caspase Inhibitors / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D012275:Oryza / Q000737:chemistry*; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D053218:Receptors, Death Domain / Q000235:genetics
chemical_list: D061945:Caspase Inhibitors; D010936:Plant Extracts; D053218:Receptors, Death Domain; D053181:Caspase 8
keywords: Apoptotic cell death; Death receptors; Fermented brown rice; Jurkat cells; Non-mitochondrial pathway; Rice bran