title: Searching in mother nature for anti-cancer activity: anti-proliferative and pro-apoptotic effect elicited by green barley on leukemia/lymphoma cells.
abstract: Green barley extract (GB) was investigated for possible anti-cancer activity by examining its anti-proliferative and pro-apoptotic properties on human leukemia/lymphoma cell lines. Our results indicate that GB exhibits selective anti-proliferative activity on a panel of leukemia/lymphoma cells in comparison to non-cancerous cells. Specifically, GB disrupted the cell-cycle progression within BJAB cells, as manifested by G2/M phase arrest and DNA fragmentation, and induced apoptosis, as evidenced by phosphatidylserine (PS) translocation to the outer cytoplasmic membrane in two B-lineage leukemia/lymphoma cell lines. The pro-apoptotic effect of GB was found to be independent of mitochondrial depolarization, thus implicating extrinsic cell death pathways to exert its cytotoxicity. Indeed, GB elicited an increase of TNF-α production, caspase-8 and caspase-3 activation, and PARP-1 cleavage within pre-B acute lymphoblastic leukemia Nalm-6 cells. Moreover, caspase-8 and caspase-3 activation and PARP-1 cleavage were strongly inhibited/blocked by the addition of the specific caspase inhibitors Z-VAD-FMK and Ac-DEVD-CHO. Furthermore, intracellular signaling analyses determined that GB treatment enhanced constitutive activation of Lck and Src tyrosine kinases in Nalm-6 cells. Taken together, these findings indicate that GB induced preferential anti-proliferative and pro-apoptotic signals within B-lineage leukemia/lymphoma cells, as determined by the following biochemical hallmarks of apoptosis: PS externalization, enhanced release of TNF-α, caspase-8 and caspase-3 activation, PARP-1 cleavage and DNA fragmentation Our observations reveal that GB has potential as an anti-leukemia/lymphoma agent alone or in combination with standard cancer therapies and thus warrants further evaluation in vivo to support these findings.
authors.affiliation: Department of Biological Sciences and Border Biomedical Research Center, the University of Texas at El Paso, El Paso, Texas, United States of America.
authors.forename: Elisa
authors.initials: E
authors.lastname: Robles-Escajeda
authors.forename: Dennise
authors.initials: D
authors.lastname: Lerma
authors.forename: Alice M
authors.initials: AM
authors.lastname: Nyakeriga
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Ross
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kirken
authors.forename: Renato J
authors.initials: RJ
authors.lastname: Aguilera
authors.forename: Armando
authors.initials: A
authors.lastname: Varela-Ramirez
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D001467:Hordeum / Q000737:chemistry*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008223:Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3
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