YM155 sensitizes HeLa cells to TRAIL-mediated apoptosis via cFLIP and survivin downregulation.

YM155 sensitizes HeLa cells to TRAIL-mediated apoptosis via cFLIP and survivin downregulation. Oncol Lett. 2020 Oct;20(4):72 Authors: Chandrasekaran AP, Poondla N, Ko NR, Oh SJ, Ramakrishna S Abstract Tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis is a safe method for the treatment of various types of cancer. However, TRAIL therapy is less effective in certain types of cancer, including cervical cancer. To address this problem, a combinatorial approach was employed to sensitize cervical cancer at low dosages. YM155, a survivin inhibitor, was used at low dosages along with TRAIL to induce apoptosis in HeLa cells. The effects of the individual treatment with TRAIL and YM155 on apoptosis were assessed by propidium iodide assay. In addition, to validate the DNA damage exhibited by the combination treatment, the phosphorylation status of γH2A histone family member X was investigated by immunofluorescence and western blot analysis. TRAIL or YM155 alone had no significant effect on DNA damage and apoptosis. However, the TRAIL/YM155 combination triggered a synergistic pro-apoptotic stimulus in HeLa cells. The mRNA and protein levels of CASP8- and FADD-like apoptosis regulator (cFLIP), death receptor 5 (DR5) and survivin were monitored using RT-PCR and western blot analysis, respectively. This combinatorial approach downregulated both mRNA and protein expression levels of cFLIP and survivin. Further experi...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research