Cathepsin L affects apoptosis of glioblastoma cells: a potential implication in the design of cancer therapeutics.
BACKGROUND
Previous studies indicate that Cathepsin L (CatL) is involved in brain tumour progression. Here, CatL in tumour cell invasion and apoptosis has been studied.


METHODS
Human glioblastoma cell line U87 was transfected with CatL cDNA in sense and antisense orientations. The in vitro invasiveness was tested in modified Boyden chambers. Apoptosis was determined by fluorescent staining, caspase activity, and by Bax and Bcl-2 mRNA levels.


RESULTS
Surprisingly, the invasiveness of U87 cells was not impaired by genetic down-regulation of CatL expression. In the CatL antisense clones, the apoptotic rate induced by either intrinsic or extrinsic stimuli was increased, whereas CatL sense transfection seemed to protect the cells from apoptosis.


CONCLUSIONS
Increased chemoresistance of tumour cells may be associated with increased levels of CatL and may have potential application in gene therapy, which would augment the apoptosis of glioblastoma cells induced by chemotherapy.
Zajc
Irena
I
Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, 1000 Ljubljana, Slovenia. irena.zajc@nib.si
Hreljac
Irena
I
Lah
Tamara
T
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D020169:Caspases / Q000378:metabolism; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D016373:DNA, Antisense / Q000235:genetics / Q000494:pharmacology; D015195:Drug Design; D004797:Enzyme-Linked Immunosorbent Assay; D015316:Genetic Therapy; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006801:Humans; D009361:Neoplasm Invasiveness; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D016373:DNA, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D002403:Cathepsins; D020169:Caspases; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L