title: Synthetic chenodeoxycholic acid derivatives inhibit glioblastoma multiform tumor growth in vitro and in vivo.
abstract: We previously reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis-inducing activity on various cancer cells in vitro. This study was undertaken to explore whether synthetic CDCA derivatives, HS-1199 and HS-1200, had an anticancer effect on malignant glioblastoma cells. We administered them in culture to U-118MG, U-87MG, T98G, and U-373MG cells. The tested glioblastoma cells showed several lines of apoptotic manifestations, such as activation of caspase-3, degradation of DFF, production of poly(ADP-ribose) polymerase cleavage, nuclear condensation, inhibition of proteasome activity, reduction of mitochondrial membrane potential and the release of cytochrome c to cytosol and translocation of AIF to nuclei. Between the two synthetic derivatives, HS-1200 showed a stronger apoptosis-inducing effect than HS-1199. In vivo efficacy of HS-1200 was tested in U87MG cells inoculated into non-obese diabetic and severe combined immunodeficient (NOD/SCID) mice. The HS-1200 treatment significantly inhibited the increase of tumor size in NOD/SCID mice and prolonged the life spans. This study supports the possibility of synthetic CDCA derivatives as a potential chemotherapeutic agent.
authors.affiliation: Medical Science Research Center and College of Medicine (BK21 program), Dong-A University, Busan 602-714, South Korea.
authors.forename: Su-Bog
authors.initials: SB
authors.lastname: Yee
authors.forename: Won Jae
authors.initials: WJ
authors.lastname: Yeo
authors.forename: Bong Soo
authors.initials: BS
authors.lastname: Park
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Baek
authors.forename: Yoon Cheong
authors.initials: YC
authors.lastname: Kim
authors.forename: Su Young
authors.initials: SY
authors.lastname: Seo
authors.forename: Sang Hwa
authors.initials: SH
authors.lastname: Lee
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Kim
authors.forename: Hongsuk
authors.initials: H
authors.lastname: Suh
authors.forename: Nam Deuk
authors.initials: ND
authors.lastname: Kim
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Lim
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Yoo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D016019:Survival Analysis; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: C479128:HS 1200; C503536:HS-1199; D002635:Chenodeoxycholic Acid; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases