title: 2'-hydroxyflavanone induces apoptosis of human osteosarcoma 143 B cells by activating the extrinsic TRAIL- and intrinsic mitochondria-mediated pathways.
abstract: Flavanones demonstrate a propensity to antiproliferation and induce apoptosis of malignant cells. Among the 4 flavanones under study, 2'-hydroxyflavanone exhibited the greatest potency to reduce the cell viability of 143 B cells in 4 osteosarcoma cells. Flow cytometry analysis showed that 2'-hydroxyflavanone increased the hypodiploid cells in the sub-G1 phase but resulted in the reduced DNA content in the G0/G1 phase in 143 B cells. The 2'-hydroxyflavanone-induced apoptosis in 143 B cells was confirmed by 4'-6-diamidino-2-phenylindole staining and mitochondrial membrane potential (Δψm) assay. Increasing expressions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and death receptor 5 (DR5) were found in 2'-hydroxyflavanone-treated cells. Moreover, 2'-hydroxyflavanone increased the expressions of B-cell lymphoma-extra small, cytochrome c, and cleavage poly (ADP-ribose) polymerase but downregulated B-cell lymphoma/leukemia-2expressions in 143 B cells. Furthermore, in vivo experiments showed that 2'-hydroxyflavanone inhibited the tumor growth of 143 B cells. 2'-hydroxyflavanone induced the apoptosis of 143 B cells via the extrinsic TRAIL- and intrinsic mitochondrial-dependent pathways, indicating its potential for inducing cancer apoptosis in osteosarcoma.
authors.affiliation: a Department of Orthopedics, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung, Taiwan and School of Medicine , Chung Shan Medical University , Taichung , Taiwan.
authors.forename: Ko-Hsiu
authors.initials: KH
authors.lastname: Lu
authors.forename: Pei-Ni
authors.initials: PN
authors.lastname: Chen
authors.forename: Ko-Huang
authors.initials: KH
authors.lastname: Lue
authors.forename: Ming-Tsung
authors.initials: MT
authors.lastname: Lai
authors.forename: Meng-Shian
authors.initials: MS
authors.lastname: Lin
authors.forename: Yih-Shou
authors.initials: YS
authors.lastname: Hsieh
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Chu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*
chemical_list: C520534:2'-hydroxyflavanone; D044950:Flavanones; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases