PMID- 32863905
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 1792-1074 (Print)
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Linking)
VI  - 20
IP  - 4
DP  - 2020 Oct
TI  - YM155 sensitizes HeLa cells to TRAIL-mediated apoptosis via cFLIP and survivin 
      downregulation.
PG  - 72
LID - 10.3892/ol.2020.11933 [doi]
LID - 72
AB  - 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 gammaH2A 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 
      experimental results suggested that the combination treatment significantly 
      reduced cell viability, invasion and migration of HeLa cells. Overall, the 
      present findings indicated that the low dosage of YM155 sensitized HeLa cells to 
      TRAIL-induced apoptosis via a mechanism involving downregulation of cFLIP and 
      survivin. The results indicated the importance of combination drug treatment and 
      reveal an effective therapeutic alternative for TRAIL therapy in human cervical 
      cancer.
CI  - Copyright: (c) Chandrasekaran et al.
FAU - Chandrasekaran, Arun Pandian
AU  - Chandrasekaran AP
AD  - Graduate School of Biomedical Science and Engineering, Department of Biomedical 
      Science, Hanyang University, Seoul 04763, Republic of Korea.
FAU - Poondla, Naresh
AU  - Poondla N
AD  - Graduate School of Biomedical Science and Engineering, Department of Biomedical 
      Science, Hanyang University, Seoul 04763, Republic of Korea.
FAU - Ko, Na Re
AU  - Ko NR
AD  - Biomedical Research Center, Asan Institute for Life Sciences, Seoul 05505, 
      Republic of Korea.
AD  - Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College 
      of Medicine, Seoul 05505, Republic of Korea.
FAU - Oh, Seung Jun
AU  - Oh SJ
AD  - Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College 
      of Medicine, Seoul 05505, Republic of Korea.
FAU - Ramakrishna, Suresh
AU  - Ramakrishna S
AD  - Graduate School of Biomedical Science and Engineering, Department of Biomedical 
      Science, Hanyang University, Seoul 04763, Republic of Korea.
AD  - College of Medicine, Department of Genetics, Hanyang University, Seoul 04763, 
      Republic of Korea.
LA  - eng
PT  - Journal Article
DEP - 20200730
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC7436932
OTO - NOTNLM
OT  - CASP8- and FADD-like apoptosis regulator
OT  - HeLa cells
OT  - YM155
OT  - apoptosis
OT  - death receptor 5
OT  - survivin
OT  - tumor necrosis factor-related apoptosis inducing ligand therapy
EDAT- 2020/08/31 06:00
MHDA- 2020/08/31 06:01
PMCR- 2020/07/30
CRDT- 2020/09/01 06:00
PHST- 2020/02/19 00:00 [received]
PHST- 2020/06/16 00:00 [accepted]
PHST- 2020/09/01 06:00 [entrez]
PHST- 2020/08/31 06:00 [pubmed]
PHST- 2020/08/31 06:01 [medline]
PHST- 2020/07/30 00:00 [pmc-release]
AID - OL-0-0-11933 [pii]
AID - 10.3892/ol.2020.11933 [doi]
PST - ppublish
SO  - Oncol Lett. 2020 Oct;20(4):72. doi: 10.3892/ol.2020.11933. Epub 2020 Jul 30.