Anion exchanger inhibitor DIDS induces human poorly-differentiated malignant hepatocellular carcinoma HA22T cell apoptosis.
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.
Liu
Chung-Jung
CJ
Institute of Biochemistry and Biotechnology, Medical College, Chung Shan Medical University, No. 110, Sect. 1, Chen-Kuo N. Road, Taichung 402, Taiwan.
Hwang
Jin-Ming
JM
Wu
Trang-Tiau
TT
Hsieh
Yi-Hsien
YH
Wu
Cheng-Chung
CC
Hsieh
Yih-Shou
YS
Tsai
Chang-Hai
CH
Wu
Hsi-Chin
HC
Huang
Chih-Yang
CY
Liu
Jer-Yuh
JY
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*
D007211:Indoles; C007293:DAPI; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid