M. Jo et al., Apoptosis induced in normal human hepatocytes by tumor necrosis factor-related apoptosis-inducing ligand, NAT MED, 6(5), 2000, pp. 564-567
Citations number
24
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been re
ported to induce apoptosis in various tumor cells but not in nontransformed
, normal cells(1-3). Preclinical studies in mice and nonhuman primates have
shown that administration of TRAIL can induce apoptosis in human tumors, b
ut that no cytotoxicity to normal organs or tissues is found(3,4). The susc
eptibility of tumor cells to TRAIL and an apparent lack of activity in norm
al cells has lead to a proposal to use TRAIL in cancer therapy. Here, we as
sessed the sensitivity of hepatocytes from rat, mouse, rhesus monkey and hu
man livers to TRAIL-induced apoptosis. TRAIL induced apoptosis in normal hu
man hepatocytes in culture but not in hepatocytes isolated from the other s
pecies. Human hepatocytes showed characteristic features of apoptosis, incl
uding cytoplasmic shrinkage, the activation of caspases and DNA fragmentati
on. Apoptosis and cell death in human hepatocytes was massive and rapid, oc
curring in more than 60% of the cells exposed to TRAIL within 10 hours. The
se results indicate that there are species differences in sensitivity to TR
AIL, and that substantial liver toxicity might result if TRAIL were used in
human cancer therapy.