Drug repurposing as an antitumor agent: Disulfiram-mediated carbonic anhydrase 12 and anion exchanger 2 modulation to inhibit cancer cell migration

Soyoung Hwang, Dong Min Shin, Jeong Hee Hong

Research output: Contribution to journalArticle

Abstract

Disulfiram has been used in the treatment of alcoholism and exhibits an anti-tumor effect. However, the intracellular mechanism of anti-tumor activity of Disulfiram remains unclear. In this study, we focused on the modulatory role of Disulfiram via oncogenic factor carbonic anhydrase CA12 and its associated transporter anion exchanger AE2 in lung cancer cell line A549. The surface expression of CA12 and AE2 were decreased by Disulfiram treatment with a time-dependent manner. Disulfiram treatment did not alter the expression of Na+-bicarbonate cotransporters, nor did it affect autophagy regulation. The chloride bicarbonate exchanger activity of A549 cells was reduced by Disulfiram treatment in a time-dependent manner without change in the resting pH level. The expression and activity of AE2 and the expression of CA12 were also reduced by Disulfiram treatment in the breast cancer cell line. An invasion assay and cell migration assay revealed that Disulfiram attenuated the invasion and migration of A549 cells. In conclusion, the attenuation of AE2 and its supportive enzyme CA12, and the inhibitory effect on cell migration by Disulfiram treatment in cancer cells provided the molecular evidence supporting the potential of Disulfiram as an anticancer agent.

Original languageEnglish
Article number3409
JournalMolecules
Volume24
Issue number18
DOIs
Publication statusPublished - 2019 Sep 19

Fingerprint

Drug Repositioning
Chloride-Bicarbonate Antiporters
carbonic anhydrase
Disulfiram
exchangers
Antineoplastic Agents
Cell Movement
drugs
cancer
Cells
Modulation
anions
modulation
Pharmaceutical Preparations
Neoplasms
cells
cultured cells
carbonates
tumors
transporter

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Cite this

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abstract = "Disulfiram has been used in the treatment of alcoholism and exhibits an anti-tumor effect. However, the intracellular mechanism of anti-tumor activity of Disulfiram remains unclear. In this study, we focused on the modulatory role of Disulfiram via oncogenic factor carbonic anhydrase CA12 and its associated transporter anion exchanger AE2 in lung cancer cell line A549. The surface expression of CA12 and AE2 were decreased by Disulfiram treatment with a time-dependent manner. Disulfiram treatment did not alter the expression of Na+-bicarbonate cotransporters, nor did it affect autophagy regulation. The chloride bicarbonate exchanger activity of A549 cells was reduced by Disulfiram treatment in a time-dependent manner without change in the resting pH level. The expression and activity of AE2 and the expression of CA12 were also reduced by Disulfiram treatment in the breast cancer cell line. An invasion assay and cell migration assay revealed that Disulfiram attenuated the invasion and migration of A549 cells. In conclusion, the attenuation of AE2 and its supportive enzyme CA12, and the inhibitory effect on cell migration by Disulfiram treatment in cancer cells provided the molecular evidence supporting the potential of Disulfiram as an anticancer agent.",
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Drug repurposing as an antitumor agent : Disulfiram-mediated carbonic anhydrase 12 and anion exchanger 2 modulation to inhibit cancer cell migration. / Hwang, Soyoung; Shin, Dong Min; Hong, Jeong Hee.

In: Molecules, Vol. 24, No. 18, 3409, 19.09.2019.

Research output: Contribution to journalArticle

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