L-carnitine sensitizes human glioblastoma cells to TRAIL-induced apoptosis / 中国药理学通报

ABSTRACT

Aim To investigate the enhancing effect of L-carnitine as a sensitizer on tumor necrosis factor-re-lated apoptosis inducing ligand ( TRAIL)-induced ap-optosis in glioma cells. Methods Glioma cell U87 was used as model cell line. Cell viability was determined by CCK-8 , and apoptosis was assessed by Annexin V-FITC/PI staining, caspase-3 activity and expres-sion. The expression and transcription of nuclear factor kappa B ( NF-κB ) and FLICE inhibiting protein ( c-FLIP) were measured by RT-PCR and Western blot. In addition, NF-κB was knockdown to analyze its regu-lating effect on c-FLIP expression. Results The com-bination treatment with TRAIL and L-carnitine signifi-cantly inhibited cell proliferation and induced apopto-sis. Compared with control, combinational treatment significantly suppressed the transcription and expres-sion of c-FLIP as well as translocation of NF-κB. Through silencing NF-κB, NF-κB was found to act as upstream signaling to regulate c-FLIP. Conclusion L-carnitine sensitizes TRAIL-induced tumor cell apoptosis via suppression of NF-κB-dependent c-FLIP expres-sion.