PMID- 23135704
OWN - NLM
STAT- MEDLINE
DCOM- 20131024
LR  - 20121126
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 42
IP  - 1
DP  - 2013 Jan
TI  - The microtubule targeting agent PBOX-15 inhibits integrin-mediated cell adhesion 
      and induces apoptosis in acute lymphoblastic leukaemia cells.
PG  - 239-46
LID - 10.3892/ijo.2012.1688 [doi]
AB  - Although recent decades have seen an improved cure rate for newly diagnosed 
      paediatric acute lymphoplastic leukaemia (ALL), the treatment options for adult 
      ALL, T-cell ALL (T-ALL) and relapsed disease remain poor. We have developed a 
      novel series of pyrrolo-1,5-benzoxazepine (PBOX) compounds and established their 
      anticancer efficacy in a variety of human tumour cell types. Here, we demonstrate 
      that PBOX-15 inhibits cell growth, and induces G2/M cell cycle arrest and 
      apoptosis in both T-ALL and B-cell ALL (B-ALL) cells. In addition, prior to 
      PBOX-15-induced apoptosis, PBOX-15 decreases ALL cell adhesion, spreading and 
      migration. Concurrently, PBOX-15 differentially down-regulates beta1-, beta2- and 
      alpha4-integrin expression in ALL cells and significantly decreases integrin-mediated 
      cell attachment. PBOX-15 interferes with the lateral mobility and clustering of 
      integrins in both B-ALL and T-ALL cells. These data suggest that PBOX-15 is not 
      only effective in inducing apoptosis in ALL cells, but also has the potential to 
      disrupt integrin-mediated adhesion of malignant lymphocytes, which represents a 
      novel avenue for regulating leukaemic cell homing and migration.
FAU - Lysaght, Joanne
AU  - Lysaght J
AD  - Department of Haematology, Trinity College, Dublin, Ireland.
FAU - Verma, Navin K
AU  - Verma NK
FAU - Maginn, Elaina N
AU  - Maginn EN
FAU - Ryan, Jacqueline M
AU  - Ryan JM
FAU - Campiani, Giuseppe
AU  - Campiani G
FAU - Zisterer, Daniela M
AU  - Zisterer DM
FAU - Williams, D Clive
AU  - Williams DC
FAU - Browne, Paul V
AU  - Browne PV
FAU - Lawler, Mark P
AU  - Lawler MP
FAU - McElligott, Anthony M
AU  - McElligott AM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121106
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (4-acetoxy-5-(1-(naphthyl))naphtho(2,3-b)pyrrolo(2,1-d)(1,4)oxazepine)
RN  - 0 (Integrins)
RN  - 0 (Oxazepines)
RN  - 0 (Pyrroles)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Cell Adhesion/*drug effects
MH  - Cell Cycle Checkpoints/drug effects
MH  - Cell Movement/*drug effects
MH  - Cell Proliferation/drug effects
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - Integrins/*metabolism
MH  - Microtubules/*drug effects
MH  - Oxazepines/*pharmacology
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/metabolism/*pathology
MH  - Pyrroles/*pharmacology
MH  - Tumor Cells, Cultured
EDAT- 2012/11/09 06:00
MHDA- 2013/10/25 06:00
CRDT- 2012/11/09 06:00
PHST- 2012/08/01 00:00 [received]
PHST- 2012/09/25 00:00 [accepted]
PHST- 2012/11/09 06:00 [entrez]
PHST- 2012/11/09 06:00 [pubmed]
PHST- 2013/10/25 06:00 [medline]
AID - 10.3892/ijo.2012.1688 [doi]
PST - ppublish
SO  - Int J Oncol. 2013 Jan;42(1):239-46. doi: 10.3892/ijo.2012.1688. Epub 2012 Nov 6.