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Apoptosis in human hepatoma cell lines by chemotherapeutic drugs via Fas-dependent and Fas-independent pathways

 Shunai Jiang  ;  Moon Jung Song  ;  Eui‐Cheol Shin  ;  Mi‐Ock Lee  ;  Se Jong Kim  ;  Jeon Han Park 
 HEPATOLOGY, Vol.29(1) : 101-110, 1999 
Journal Title
Issue Date
Antibodies ; Antineoplastic Agents/pharmacology* ; Apoptosis/drug effects* ; Apoptosis/immunology ; Carcinoma, Hepatocellular/pathology* ; Cell Division/drug effects ; Cisplatin/pharmacology ; Flow Cytometry ; Fluorouracil/pharmacology ; Humans ; In Situ Nick-End Labeling ; Liver Neoplasms/pathology* ; RNA, Messenger/biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Cells, Cultured ; fas Receptor/biosynthesis ; fas Receptor/immunology ; fas Receptor/physiology*
Many chemotherapeutic drugs have been found to exert their mode of action via induction of apoptosis in cancer cells. The mechanisms involved in this process are not clear. Recent studies have shown that the Fas/Fas ligand (FasL) system is a key factor controlling apoptotic cell death. In the present study, the involvement of Fas in chemotherapeutic drug-induced apoptosis in hepatoma cell lines was investigated. Five different human hepatoma cell lines, Hep G2, Hep G2.2.15, Hep 3B, SK-Hep-1, and PLC/PRF/5, were used. It was found that they expressed different levels of Fas. However, all five cell lines were susceptible to apoptosis when treated with chemotherapeutic drugs such as 5-fluorouracil (5-FU) or cisplatin. In Hep G2 that constitutively expressed Fas, 5-FU or cisplatin treatment caused an increase in the expression of Fas before the formation of oligonucleosomal DNA fragments, a typical feature of apoptosis. However, in Hep 3B, where Fas is undetectable, apoptosis could also be induced by 5-FU or cisplatin without induction of Fas. The agonistic anti-Fas antibody (CH-11) was capable of inducing apoptosis by itself and promoted drug-induced apoptosis in Hep G2 but not in Hep 3B. The antagonistic anti-Fas antibody (ZB4) inhibited drug-induced apoptosis in Hep G2. Our results suggest that apoptosis can be induced in hepatoma cell lines via both Fas-dependent and Fas-independent pathways.
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1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Se Jong(김세종)
Park, Jeon Han(박전한) ORCID logo https://orcid.org/0000-0001-9604-3205
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