Experimental study on role of lysosomes in cancer chemotherapy.

Abstract

The lysosome has attracted much attention because of its role in the autolysis of cells, and has suggested the importance of introducing the concept of the lysosome into cancer chemotherapy. In the present study acid deoxyribonuclease, (3-glucuronidase and lysozyme in Yoshida ascites tumor cells were proved to be lysosomal enzym~s because of the high latency in their activities and their characteristic intracellular distribution patterns. However, acid phosphatase was not characteristic in these respects, so that it is not reasonable to estimate the behaviors of lysosomes in Yoshida ascites tumor cells only by the activity of this enzyme. Since the membranes bounding Iysosomes have been assumed to be lipoprotein in nature, it was investigated whether lipoprotein lipase (LPL) could labilize lysosomes in tumor cells and it was found that LPL could be a strong lysosome labilizer in vitro and in vivo. A combined treatment with LPL and mitomycin.C (MMC) brought more remarkable changes in lysosomes of tumor cells than MMC alone. The membrane stability of lysosomes in tumor cells against LPL was less than that in liver cells of tumor-bearing rats, suggesting no enhancement of toxicity in the combination therapy with LPL and antitumor agents. The survival experiment showed that the cytocidal effect of MMC was etlhanced by LPL. Based on these experimental findings clinical trials of combination chemotherapy with antitumor agents and lysosome lahilizers are under investigation.