Effect of vitamin E and human placenta cysteine peptidase inhibitor on expression of cathepsins B and L in implanted hepatoma Morris 5123 tumor model in Wistar rats.
OBJECTIVE
To examine the effectiveness of human placental inhibitors, by injecting vitamin E to rats with transplanted Morris-5123 hepatoma, on the expression of cathepsins B and L in tumor, liver, lung and blood sera after transplantation of Morris 5123 hepatoma.


METHODS
Animals were divided into 10 groups receiving three different concentrations of vitamin E and inhibitors along or in combination and compared with negative control (healthy rats) and positive control (tumor rats). Effectiveness of treatment was evaluated with regard to survival time, tumor response and determination of the activities of proteolytic enzymes and their inhibitors using flurogenic substrates.


RESULTS
Cathepsins B and L activities were elevated by 16-fold in comparison with negative control tissues, and their endogenous inhibitor activity decreased by 1.2-fold before treatment. In several cases, tumors completely disappeared following vitamin E plus human placental cyteine protease inhibitor (CPI) compared with controls. The number of complete tumor responses was higher when 20 m/kg vitamin E plus 400 microg of CPI was used, i.e. 7/10 rats survived more than two mo. Cathepsins B and L were expressed significantly in tumor, liver, lung tissues and sera in parallel to the increasing of the endogenous inhibitor activity compared with the controls after treatment (P<0.0001).


CONCLUSIONS
The data indicate formation of metastasis significantly reduced in treated rats, which might provide a therapeutic basis for anti-cancer therapy.
Sebzda
Tadeusz
T
Department of Pathophysiology, Medical University of Wroclaw, Poland.
Hanczyc
Piotr
P
Saleh
Yousif
Y
Akinpelumi
Bernice-F
BF
Siewinski
Maciej
M
Rudnicki
Jerzy
J
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002401:Cathepsin B / Q000378:metabolism*; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism*; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D009368:Neoplasm Transplantation; D010920:Placenta / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D015853:Cysteine Proteinase Inhibitors; D014810:Vitamin E; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C534280:Ctsl protein, rat