Cyclophilin A as a New Therapeutic Target for Hepatitis C Virus-induced Hepatocellular Carcinoma.
10.4196/kjpp.2013.17.5.375
- Author:
Jinhwa LEE
1
Author Information
1. Department of Clinical Lab Science, School of Health Science, Dongseo University, Busan 617-716, Korea. jinhwa2000@gdsu.dongseo.ac.kr
- Publication Type:Review
- Keywords:
Cyclophilin A;
Hepatitis C virus;
Hepatocellular carcinoma;
Peptidyl prolyl isomerase
- MeSH:
Carcinoma, Hepatocellular*;
Carrier Proteins;
Cyclophilin A*;
Cyclophilins;
Cyclosporine;
Cyclosporins;
Cytosol;
Hepacivirus*;
Hepatitis B virus;
Hepatitis C*;
Hepatitis C, Chronic;
Hepatitis;
Hepatocytes;
Liver;
Liver Diseases;
Liver Neoplasms;
RNA Replicase
- From:The Korean Journal of Physiology and Pharmacology
2013;17(5):375-383
- CountryRepublic of Korea
- Language:English
-
Abstract:
Hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is thought to account for more than 80% of primary liver cancers. Both HBV and HCV can establish chronic liver inflammatory infections, altering hepatocyte and liver physiology with potential liver disease progression and HCC development. Cyclophilin A (CypA) has been identified as an essential host factor for the HCV replication by physically interacting with the HCV non structural protein NS5A that in turn interacts with RNA-dependent RNA polymerase NS5B. CypA, a cytosolic binding protein of the immunosuppressive drug cyclosporine A, is overexpressed in many cancer types and often associated with malignant transformation. Therefore, CypA can be a good target for molecular cancer therapy. Because of antiviral activity, the CypA inhibitors have been tested for the treatment of chronic hepatitis C. Nonimmunosuppressive Cyp inhibitors such as NIM811, SCY-635, and Alisporivir have attracted more interests for appropriating CypA for antiviral chemotherapeutic target on HCV infection. This review describes CypA inhibitors as a potential HCC treatment tool that is contrived by their obstructing chronic HCV infection and summarizes roles of CypA in cancer development.
