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Anion exchanger inhibitor DIDS induces human poorly-differentiated malignant hepatocellular carcinoma HA22T cell apoptosis

  • 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
Article

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.

Keywords

HA22T hepatocellular carcinoma cells Anion exchanger 2 DIDS Apoptosis Proliferation Anion transport activity 

Notes

Acknowledgments

This work was supported in part by grants from the National Science Council, Republic of China (NSC 95–2320-B-040-043) and from Chung Shan Medical University, Republic of China (CSMU 95-OM-A-110, CSMU 95-OM-B-009 and CSMU 95-OM-B-027).

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Copyright information

© Springer Science+Business Media, LLC. 2007

Authors and Affiliations

  • Chung-Jung Liu
    • 1
  • Jin-Ming Hwang
    • 2
  • Trang-Tiau Wu
    • 3
  • Yi-Hsien Hsieh
    • 1
  • Cheng-Chung Wu
    • 4
  • Yih-Shou Hsieh
    • 1
  • Chang-Hai Tsai
    • 5
  • Hsi-Chin Wu
    • 6
  • Chih-Yang Huang
    • 7
    • 8
    • 9
  • Jer-Yuh Liu
    • 1
  1. 1.Institute of Biochemistry and Biotechnology, Medical CollegeChung Shan Medical UniversityTaichungTaiwan
  2. 2.School of Applied Chemistry, Health Care and Management College Chung Shan Medical UniversityTaichungTaiwan
  3. 3.Department of Surgery, School of Medicine, Medical College Chung Shan Medical UniversityTaichungTaiwan
  4. 4.Department of General SurgeryTaichung Veterans General Hospital TaichungTaiwan
  5. 5.Department of Healthcare Administration Asia UniversityTaichungTaiwan
  6. 6.School of medicineChina Medical University and HospitalTaichungTaiwan
  7. 7.Graduate Institute of Chinese Medical ScienceChina Medical UniversityTaichungTaiwan
  8. 8.Institute of Medical Science China Medical UniversityTaichungTaiwan
  9. 9.Department of Health and Nutrition BiotechnologyAsia UniversityTaichungTaiwan

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