PMID- 22760199
OWN - NLM
STAT- MEDLINE
DCOM- 20121018
LR  - 20171116
IS  - 1423-0232 (Electronic)
IS  - 0030-2414 (Linking)
VI  - 83
IP  - 2
DP  - 2012
TI  - Sensitization of glioma cells by X-linked inhibitor of apoptosis protein 
      knockdown.
PG  - 75-82
LID - 10.1159/000337978 [doi]
AB  - OBJECTIVE: Glioblastomas are a kind of cancer with high resistance to treatments, 
      requiring more efficient alternatives of treatment. X-linked inhibitor of 
      apoptosis (XIAP) is highly expressed in gliomas and, due to its inhibition of 
      caspases, can participate in resistance to therapy. Here we test the 
      sensitization of glioma cells with XIAP gene knockdown (KD) to drugs used in 
      chemotherapy. METHODS: We silenced XIAP expression in U87MG glioblastoma using 
      stable shRNA, and cells were treated with taxol, BCNU, temozolomide, cisplatin, 
      etoposide, resveratrol (Rsv), vincristine and doxorubicin. We analyzed cell 
      viability, cell cycle, apoptosis and senescence. RESULTS: XIAP KD cells were more 
      sensitive to etoposide, Rsv, vincristine and doxorubicin compared to wild-type 
      (WT) cells. Doxorubicin 1 microM and vincristine 100 nM induced higher activation of 
      caspases after 24 h and doxorubicin induced a higher degree of senescence 
      induction in XIAP KD cells in relation to WT cells. Phospho-p53 and phospho-H2Ax 
      Western blot indicate subsequent DNA damage as an important effector of 
      doxorubicin-induced death. CONCLUSIONS: This study suggests that XIAP inhibitors 
      may sensitize gliomas to certain drugs and induce death and that the mechanisms 
      of sensitization involve apoptosis, senescence and p53 signaling.
CI  - Copyright (c) 2012 S. Karger AG, Basel.
FAU - Lopez, Patricia L C
AU  - Lopez PL
AD  - Biophysics Department and Center of Biotechnology, Federal University of Rio 
      Grande do Sul, Porto Alegre, Brazil.
FAU - Filippi-Chiela, Eduardo C
AU  - Filippi-Chiela EC
FAU - Silva, Andrew O
AU  - Silva AO
FAU - Cordero, Elvira A A
AU  - Cordero EA
FAU - Garcia-Santos, Daniel
AU  - Garcia-Santos D
FAU - Pelegrini, Alessandra L
AU  - Pelegrini AL
FAU - Reder, Gleice M
AU  - Reder GM
FAU - Barbieri, Nicolle L
AU  - Barbieri NL
FAU - Lenz, Guido
AU  - Lenz G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120629
PL  - Switzerland
TA  - Oncology
JT  - Oncology
JID - 0135054
RN  - 0 (Antineoplastic Agents)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (X-Linked Inhibitor of Apoptosis Protein)
RN  - 0 (XIAP protein, human)
RN  - 5J49Q6B70F (Vincristine)
RN  - 6PLQ3CP4P3 (Etoposide)
RN  - 80168379AG (Doxorubicin)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis/drug effects/genetics
MH  - Caspases/metabolism
MH  - Cellular Senescence/drug effects/genetics
MH  - Central Nervous System Neoplasms/*drug therapy/*genetics
MH  - DNA Damage
MH  - Doxorubicin/pharmacology
MH  - Drug Resistance, Neoplasm
MH  - Etoposide/pharmacology
MH  - Gene Knockdown Techniques
MH  - Glioma/*drug therapy/*genetics
MH  - Humans
MH  - RNA, Small Interfering
MH  - Tumor Suppressor Protein p53/metabolism
MH  - Vincristine/pharmacology
MH  - X-Linked Inhibitor of Apoptosis Protein/*genetics/metabolism
EDAT- 2012/07/05 06:00
MHDA- 2012/10/19 06:00
CRDT- 2012/07/05 06:00
PHST- 2011/08/02 00:00 [received]
PHST- 2012/03/06 00:00 [accepted]
PHST- 2012/07/05 06:00 [entrez]
PHST- 2012/07/05 06:00 [pubmed]
PHST- 2012/10/19 06:00 [medline]
AID - 000337978 [pii]
AID - 10.1159/000337978 [doi]
PST - ppublish
SO  - Oncology. 2012;83(2):75-82. doi: 10.1159/000337978. Epub 2012 Jun 29.