title: Anion exchanger inhibitor DIDS induces human poorly-differentiated malignant hepatocellular carcinoma HA22T cell apoptosis.
abstract: Anion exchangers (AEs) of the Cl(-)/HCO3(-) exchanger family contribute to the regulation of intracellular acid-base balance. Recently, we found that anion exchanger 2 (AE2) was significantly expressed in human hepatocellular carcinoma (HCC) and in poorly-differentiated human HCC HA22T/VGH cells. In the present study, we further explored the pharmacological function of AE in four human HCC cell lines (SK-Hep-1, HA22T/VGH, HepG2, and Hep3B) following the treatment of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), an AEs specific inhibitor. After administrations with 400-1000 microM of DIDS, cell proliferation was greatly inhibited in a dose-dependent manner from 47.5 to 65.0% in higher malignant HA22T/VGH cells, but not in other cell lines. The results of 4,6-diamidino-2-phenylindole (DAPI) staining, DNA fragmentation and flow cytometric analysis further revealed that cell apoptosis induced by DIDS was also observed in HA22T/VGH cells. Therefore, these findings suggested that AE may be involved, in part, in the proliferation and survival of HA22T cells and could be a new potential therapeutic target against specific human HCC.
authors.affiliation: Institute of Biochemistry and Biotechnology, Medical College, Chung Shan Medical University, No. 110, Sect. 1, Chen-Kuo N. Road, Taichung 402, Taiwan.
authors.forename: Chung-Jung
authors.initials: CJ
authors.lastname: Liu
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Hwang
authors.forename: Trang-Tiau
authors.initials: TT
authors.lastname: Wu
authors.forename: Yi-Hsien
authors.initials: YH
authors.lastname: Hsieh
authors.forename: Cheng-Chung
authors.initials: CC
authors.lastname: Wu
authors.forename: Yih-Shou
authors.initials: YS
authors.lastname: Hsieh
authors.forename: Chang-Hai
authors.initials: CH
authors.lastname: Tsai
authors.forename: Hsi-Chin
authors.initials: HC
authors.lastname: Wu
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.forename: Jer-Yuh
authors.initials: JY
authors.lastname: Liu
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001692:Biological Transport / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D007211:Indoles; D008113:Liver Neoplasms / Q000473:pathology*
chemical_list: D007211:Indoles; C007293:DAPI; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid