ClC-3 chloride channel protein induces G1�arrest in hepatocellular carcinoma Hep3B cells

Abstract

ClC-3 is a type of chloride channel that has multiple functions in tumorigenesis and tumor growth, and can be blocked by DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid). In the present study, we found that DIDS inhibited the proliferation of Hep3B hepatocellular carcinoma (HCC) cells in a concentration-dependent manner. More in-depth research demonstrated that DIDS downregulated the protein expression levels of cyclin D1 and cyclin E, which are key proteins of the G1 phase. Additionally, we found that ClC-3 siRNA transfection induced G1 arrest in the Hep3B cells, confirming that ClC-3 is involved in the DIDS-induced inhibition of Hep3B cells. Moreover, the level of α-fetoprotein (AFP), a negative prognostic indicator of HCC, was decreased after treatment with DIDS and ClC-3 siRNA. In conclusion, we demonstrated that ClC-3 can arrest the cell cycle at the G1 phase to inhibit cell proliferation, suggesting that ClC-3 has the potential to be a novel target for HCC therapy and potentially improve the prognosis of HCC patients.

Chloride intracellular channels as novel biomarkers for digestive system tumors (Review)

“…It is not clear whether CLICs act as ion channels to affect liver cancer. Of note, the chloride channel blocker 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) can effectively inhibit the proliferation of liver cancer cells (99). DIDS induces G1 arrest by downregulating the protein expression levels of cyclin D1 and cyclin E (99).…”

“…Of note, the chloride channel blocker 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) can effectively inhibit the proliferation of liver cancer cells (99). DIDS induces G1 arrest by downregulating the protein expression levels of cyclin D1 and cyclin E (99). DIDS reduces the protein expression levels of α-fetoprotein, suggesting that it may be able to improve the prognosis of HCC in patients (99).…”

“…DIDS induces G1 arrest by downregulating the protein expression levels of cyclin D1 and cyclin E (99). DIDS reduces the protein expression levels of α-fetoprotein, suggesting that it may be able to improve the prognosis of HCC in patients (99). CLIC1 has a vital role, similar to that of proto-oncogene, that may be targeted in the development of novel tumor treatments with chloride channel blocker IAA-94 (100).…”