title: Synthetic chenodeoxycholic acid derivative HS-1200-induced apoptosis of p815 mastocytoma cells is augmented by co-treatment with lactacystin.
abstract: The antitumor activity of a synthetic chenodeoxycholic acid derivative, HS-1200, on the p815 mastocytoma cell line was investigated. We present several lines of evidence indicating that HS-1200 at 35 microM induced apoptosis of p815 cells. Reduction of mitochondrial membrane potential, the release of cytochrome to cytosol, activation of caspase-3, nuclear condensation, production of poly(ADP-ribose) polymerase cleavage, generation of DNA fragmentation and nuclear condensation were demonstrated. Importantly, HS-1200 inhibited proteasome activity. Next, the combination treatment of HS-1200 or a proteasome inhibitor lactacystin was undertaken. Although the single treatment of 20 microM HS-1200 or 1 microM lactacystin induced apoptosis slightly, the combination treatment of them augmented prominently the extent of apoptosis. The combination therapy of HS-1200 and lactacystin could be potentially a therapeutic strategy reducing the extent and severity of treatment-related toxicity.
authors.affiliation: Department of Microbiology and Immunology, Dong-A University College of Medicine and Institute of Medical Science, Seo Gu, Busan, South Korea.
authors.forename: Su Yeong
authors.initials: SY
authors.lastname: Seo
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Jun
authors.forename: Sung Moon
authors.initials: SM
authors.lastname: Jung
authors.forename: Ki-Ho
authors.initials: KH
authors.lastname: Kim
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Lim
authors.forename: Bong Soo
authors.initials: BS
authors.lastname: Park
authors.forename: Jae-Kon
authors.initials: JK
authors.lastname: Kim
authors.forename: Sungeun
authors.initials: S
authors.lastname: Lee
authors.forename: Hongsuk
authors.initials: H
authors.lastname: Suh
authors.forename: Nam Deuk
authors.initials: ND
authors.lastname: Kim
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Yoo
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D053938:DNA Fragmentation; D004357:Drug Synergism; D034801:Mastocytoma; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009097:Multienzyme Complexes / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex
chemical_list: D000970:Antineoplastic Agents; C479128:HS 1200; D009097:Multienzyme Complexes; D002635:Chenodeoxycholic Acid; C067713:lactacystin; D011065:Poly(ADP-ribose) Polymerases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine