Selective induction of apoptosis in Hep 3B cells by topoisomerase I inhibitors: evidence for a protease-dependent pathway that does not activate cysteine protease P32.

Serine protease inhibitor TPCK prevents Taxol-induced cell death and blocks c-Raf-1 and Bcl-2 phosphorylation in human breast carcinoma cells

“…etoposide, UCN-01, and daunorubicin) in cells of hematopoietic origin Mansat et al, 1997;Shao et al, 1997;Sebestyen et al, 1997;Lotem and Sachs, 1996). TLCK on the other hand, was found to be e ective in inhibiting cell death by camptothecin and glycodeoxycholate in hepatocytes, but TPCK was without e ect (Kwo et al, 1995, Adjei et al, 1996. Thus, it is likely that the role of speci®c serine proteases is dependent on both the cell type and agent examined.…”

“…Although the role of serine proteases in cell death remains largely unexplored, a number of studies have shown that serine protease inhibitors can block apoptosis induced by certain stimuli Adjei et al, 1996, Dong et al, 1997Chow et al, 1995;Weis et al, 1995;Mansat et al, 1997;Shao et al, 1997). For example, TPCK has been shown to inhibit both FAS antigen-and p53-induced apoptosis as well as cell death occurring in response to various chemotherapeutic agents (e.g.…”

“…The activation of caspase(s) and the cleavage of their substrates have been observed during apoptosis induced by diverse stimuli (White, 1996;Takahashi and Earnshaw, 1996;Martin and Green, 1995;Tewari et al, 1995;Salvesen and Dixit, 1997). A number of recent studies have shown that various serine protease inhibitors can also abrogate cell death induced by certain stimuli Wright et al, 1997;Adjei et al, 1996). This suggests that serine proteases are also likely to play a role in the apoptotic process, but virtually nothing is known about the pathway.…”

Inhibition of interleukin 6-mediated mitogen-activated protein kinase activation attenuates growth of a cholangiocarcinoma cell line

“…17 The human hepatoma cell lines Hep3B were obtained from American Type Culture Collection (Rockville, MD) and cultured as previously described. 18 Measurement of IL-6 Secretion. Confluent cells cultured in 100-mm culture plates were incubated for 24 hours in medium containing 10 ng/mL IL-1␤, 10 ng/mL tumor necrosis factor ␣ (TNF-␣), or medium alone (control).…”

Fas-mediated apoptosis in mouse hepatocytes involves the processing and activation of caspases

“…[26][27][28] Little is known about how apoptosis is controlled in many of the latter organs. Hepatocytes or hepatoma cells may be induced to apoptose by cholestatic bile acids, 29 topoisomerase I inhibitors, 30 transforming growth factor ␤, 31 and tumor necrosis factor ␣. 32 Hepatocytes also express high levels of Fas antigen, which has been shown in vivo by intraperitoneal injection of anti-Fas antibody in mice to result in the death of the animals through massive liver damage.…”