TNF-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in various transformed cell lines. Therefore, we investigated TRAIL sensitivity, TRAIL-induced
nuclear factor-kappaB (
NF-kappaB) activation, and expression of TRAIL in human colonic
adenocarcinoma cell lines (HT-29, LS180, SK-CO-1). All four
TRAIL receptors (TRAIL-R1 through TRAIL-R4) are expressed in these cell lines. TRAIL sensitivity was assessed by assay of cell viability.
Cancer cell viabilities were 83 +/- 3.1% (HT-29), 90 +/- 4.3% (LS180), and 88 +/- 6.3% (SK-CO-1) at 24 hours after the addition of 100 ng/ml TRAIL, indicating that these cell lines were relatively resistant to TRAIL. Activation of
NF-kappaB was variably influenced by TRAIL administration, with no consistent tendency among the cell lines, indicating that TRAIL-induced
NF-kappaB activation might be cell-type dependent. In contrast, TRAIL was expressed in the human colonic
adenocarcinoma cell lines by Western blotting and RT-PCR. Increased expression of TRAIL on
tumor cells was observed by flow cytometry after
cytokine stimulation (IFN-gamma,
TNF-alpha) or the addition of chemotherapeutic agents (
camptothecin, doxolubicin hydrochloride). TRAIL on HT-29 cells was functional and able to induce apoptosis in Jurkat cells. Jurkat cell viability was increased by the addition of TRAILR1-R4-Fc. In the presence of various
cytokines or chemotherapeutic agents, functional TRAIL is expressed on the surface of
tumor cells, and this expressed TRAIL might contribute to
tumor immune privilege by inducing apoptosis of activated human lymphocytes.