PMID- 29698587
OWN - NLM
STAT- MEDLINE
DCOM- 20190531
LR  - 20190531
IS  - 1878-0261 (Electronic)
IS  - 1574-7891 (Print)
IS  - 1574-7891 (Linking)
VI  - 12
IP  - 7
DP  - 2018 Jun
TI  - Selective induction of cancer cell death by VDAC1-based peptides and their 
      potential use in cancer therapy.
PG  - 1077-1103
LID - 10.1002/1878-0261.12313 [doi]
AB  - Mitochondrial VDAC1 mediates cross talk between the mitochondria and other parts 
      of the cell by transporting anions, cations, ATP, Ca(2+) , and metabolites and 
      serves as a key player in apoptosis. As such, VDAC1 is involved in two important 
      hallmarks of cancer development, namely energy and metabolic reprograming and 
      apoptotic cell death evasion. We previously developed cell-penetrating 
      VDAC1-derived peptides that interact with hexokinase (HK), Bcl-2, and Bcl-xL to 
      prevent the anti-apoptotic activities of these proteins and induce cancer cell 
      death, with a focus on leukemia and glioblastoma. In this study, we demonstrated 
      the sensitivity of a panel of genetically characterized cancer cell lines, 
      differing in origin and carried mutations, to VDAC1-based peptide-induced 
      apoptosis. Noncancerous cell lines were less affected by the peptides. 
      Furthermore, we constructed additional VDAC1-based peptides with the aim of 
      improving targeting, selectivity, and cellular stability, including R-Tf-D-LP4, 
      containing the transferrin receptor internalization sequence (Tf) that allows 
      targeting of the peptide to cancer cells, known to overexpress the transferrin 
      receptor. The mode of action of the VDAC1-based peptides involves HK detachment, 
      interfering with the action of anti-apoptotic proteins, and thus activating 
      multiple routes leading to an impairment of cell energy and metabolism 
      homeostasis and the induction of apoptosis. Finally, in xenograft glioblastoma, 
      lung, and breast cancer mouse models, R-Tf-D-LP4 inhibited tumor growth while 
      inducing massive cancer cell death, including of cancer stem cells. Thus, 
      VDAC1-based peptides offer an innovative new conceptual framework for cancer 
      therapy.
CI  - (c) 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
FAU - Shteinfer-Kuzmine, Anna
AU  - Shteinfer-Kuzmine A
AD  - Department of Life Sciences, National Institute for Biotechnology in the Negev, 
      Ben-Gurion University of the Negev, Beer-Sheva, Israel.
FAU - Amsalem, Zohar
AU  - Amsalem Z
AD  - Department of Life Sciences, National Institute for Biotechnology in the Negev, 
      Ben-Gurion University of the Negev, Beer-Sheva, Israel.
FAU - Arif, Tasleem
AU  - Arif T
AUID- ORCID: 0000-0001-9881-0076
AD  - Department of Life Sciences, National Institute for Biotechnology in the Negev, 
      Ben-Gurion University of the Negev, Beer-Sheva, Israel.
FAU - Zooravlov, Alexandra
AU  - Zooravlov A
AD  - Department of Life Sciences, National Institute for Biotechnology in the Negev, 
      Ben-Gurion University of the Negev, Beer-Sheva, Israel.
FAU - Shoshan-Barmatz, Varda
AU  - Shoshan-Barmatz V
AUID- ORCID: 0000-0002-6756-4340
AD  - Department of Life Sciences, National Institute for Biotechnology in the Negev, 
      Ben-Gurion University of the Negev, Beer-Sheva, Israel.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180519
PL  - United States
TA  - Mol Oncol
JT  - Molecular oncology
JID - 101308230
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Transferrin)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 1.6.- (Voltage-Dependent Anion Channel 1)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Amino Acid Sequence
MH  - Animals
MH  - Biomarkers, Tumor/metabolism
MH  - Calcium/metabolism
MH  - Cell Death/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Dogs
MH  - Humans
MH  - Mice
MH  - Neoplasms/*drug therapy/*pathology
MH  - Neoplastic Stem Cells/drug effects/metabolism/pathology
MH  - Peptides/chemistry/pharmacology/*therapeutic use
MH  - Receptors, Transferrin/metabolism
MH  - Voltage-Dependent Anion Channel 1/*therapeutic use
MH  - Xenograft Model Antitumor Assays
PMC - PMC6026870
OTO - NOTNLM
OT  - VDAC1
OT  - apoptosis
OT  - cancer
OT  - metabolism
OT  - mitochondria
OT  - peptides
EDAT- 2018/04/27 06:00
MHDA- 2019/06/01 06:00
PMCR- 2018/06/01
CRDT- 2018/04/27 06:00
PHST- 2017/11/12 00:00 [received]
PHST- 2018/03/22 00:00 [revised]
PHST- 2018/04/15 00:00 [accepted]
PHST- 2018/04/27 06:00 [pubmed]
PHST- 2019/06/01 06:00 [medline]
PHST- 2018/04/27 06:00 [entrez]
PHST- 2018/06/01 00:00 [pmc-release]
AID - MOL212313 [pii]
AID - 10.1002/1878-0261.12313 [doi]
PST - ppublish
SO  - Mol Oncol. 2018 Jun;12(7):1077-1103. doi: 10.1002/1878-0261.12313. Epub 2018 May 
      19.