Publication: The selective anticancer activity of the endogenous inhibitor of calcium-activated neutral proteinase. A histological,...
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Date
1994
Authors
Logothetou-Rella, H.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
The cytotoxicity of an endogenous inhibitor
of calcium-activated neutral proteinase (CANP-I) was
evaluated using various mammalian tumor-derived cell
lines and human cell cultures.
The inhibitor was selectively cytotoxic to human
tumor cells from lung, bladder, melanoma and chronic
myeloid leukemia tissues, in a dose-dependent manner,
and was also cytotoxic to Walker rat tumor cells. The
inhibitor was not cytotoxic to normal human, urothelial,
fallopian tube, liver and resting white blood cells.
Cytological examination of the treated malignant cells
revealed cells with vacuolated cytoplasm, pyknotic,
hyperchromatic nuclei and membranous, granular
haematoxylinophilic extracellular matrix. The use of the
inhibitor on urothelial tumor tissues caused great
exfoliation of necrotic cells while not affecting normal
urothelial tissues.
When the inhibitor was tested on mixed cell cultures,
consisting of normal and malignant cell clones, a
selective cytotoxicity to the malignant cells occurred
allowing the normal cells to grow unaffected. Cytogenetic
and cytological examination of the remaining
cells, after the inhibitor treatment, showed normal
diploid karyotype and morphology.
The inhibitor was also tested in vivo on Wistar rats
bearing Walker tumors. Treatment with 50 Units1100 g
i.p. daily for 5 days caused 90% tumor regression and
necrosis of metastatic foci in the liver and abdomen,
without toxic side effects.
The protease inhibitors trypsin-chymotrypsin,
aprotinin, leupeptin and E64 were also tested in vitro and
showed no anticancer activity. In conclusion, the
endogenous inhibitor of CANP selectively killed
malignant cells of different chromosomal abnormalities,
tissue and species origin; also nuclear vlimata and
chemoresistant cells. These results are discussed in the
context of a model for the action of the endogenous
inhibitor of CANP, extracellular matrix and nuclear
Offprint requests to: Dr. Helen Logothetou-Rella, Department of
Experimental Physiology, Medical School, University of Athens. P.O.
Box 601 14, GR-153 10 Agia Paraskevi, Athens, Greece
vlimata.
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