Anion exchanger inhibitor DIDS induces human poorly-differentiated malignant hepatocellular carcinoma HA22T cell apoptosis |
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| Authors: | Chung-Jung Liu Jin-Ming Hwang Trang-Tiau Wu Yi-Hsien Hsieh Cheng-Chung Wu Yih-Shou Hsieh Chang-Hai Tsai Hsi-Chin Wu Chih-Yang Huang Jer-Yuh Liu |
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| Affiliation: | (1) Institute of Biochemistry and Biotechnology, Medical College, Chung Shan Medical University, No. 110, Sect. 1, Chen-Kuo N. Road, Taichung, 402, Taiwan;(2) School of Applied Chemistry, Health Care and Management College, Chung Shan Medical University, Taichung, 402, Taiwan;(3) Department of Surgery, School of Medicine, Medical College, Chung Shan Medical University, Taichung, 402, Taiwan;(4) Department of General Surgery, Taichung Veterans General Hospital, Taichung, 407, Taiwan;(5) Department of Healthcare Administration, Asia University, Taichung, 413, Taiwan;(6) School of medicine, China Medical University and Hospital, Taichung, 404, Taiwan;(7) Graduate Institute of Chinese Medical Science, China Medical University, Taichung, 404, Taiwan;(8) Institute of Medical Science, China Medical University, Taichung, 404, Taiwan;(9) Department of Health and Nutrition Biotechnology, Asia University, Taichung, 413, Taiwan |
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| 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 μM 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. The authors Chih-Yang Huang and Jer-Yuh Lin contributed equally to this article. |
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| Keywords: | HA22T hepatocellular carcinoma cells Anion exchanger 2 DIDS Apoptosis Proliferation Anion transport activity |
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