Effect of cysteine protease inhibitor Ep-475 on TNF-alpha-independent cyclophosphamide-induced apoptosis in mouse lymphosarcoma LS cells.
Cyclophosphamide 1.5-2.0-fold increased activity of cathepsins B and L in tumor tissue of mouse lymphosarcoma LS and caused tumor regression. The effect was most pronounced on day 5 after treatment. Twofold treatment with a selective cathepsin inhibitor Ep-475 slightly stimulated tumor growth in control mice and significantly reduced the antitumor effect of cyclophosphamide. Lysosomal cysteine proteases cathepsins B and L are involved, but do not play a key role in TNF-alpha-independent apoptosis in LS cells induced by cyclophosphamide.
Zhanaeva
S Ya
SY
Institute of Physiology, Siberian Division of the Russian Academy of Medical Sciences, Novosibirsk. djsja@mail.ru
Korolenko
T A
TA
Khoshchenko
O M
OM
Spiridonov
V K
VK
Nikolin
V P
VP
Kaledin
V I
VI
D000818:Animals; D017209:Apoptosis; D002401:Cathepsin B / Q000037:antagonists & inhibitors*; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D003520:Cyclophosphamide / Q000494:pharmacology; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008228:Lymphoma, Non-Hodgkin / Q000201:enzymology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015853:Cysteine Proteinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; C032425:N-(N-(3-carboxyoxirane-2-carbonyl)leucyl)isoamylamine; D003520:Cyclophosphamide; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534278:Ctsl protein, mouse; D007930:Leucine