Affordable Access

Tumour necrotisation in nude mice xenografts by the reversible protein synthesis inhibitor zilascorb(2H).

Authors
  • Pettersen, E O
  • Larsen, R O
  • Dornish, J M
  • Børretzen, B
  • Juul, M E
  • Aastveit, T E
  • Nesland, J M
  • Rofstad, E K
  • Oftebro, R
Type
Published Article
Journal
British journal of cancer
Publication Date
Apr 01, 1993
Volume
67
Issue
4
Pages
650–656
Identifiers
PMID: 8471421
Source
Medline
License
Unknown

Abstract

The deuterated benzaldehyde derivative zilascorb(2H), 5,6-O-benzylidene-d-L-ascorbic acid, was administered once daily by i.v. injection in nude mice with grafted tumours of a human malignant melanoma (E.E.) and ovarian carcinoma (OVCAR-3) origins. Like benzaldehyde, zilascorb(2H) has been shown to induce protein synthesis inhibition at otherwise non-toxic doses in cells grown in vitro, and acts reversibly in the sense that protein synthesis returns to normal shortly after removal of the drug. The present data indicate that daily injections with zilascorb(2H) induce a tumour volume growth inhibitory effect in both tumour xenografts studied. Furthermore, from histological examinations of each single tumour it was found that tumours of drug-treated animals, although smaller than those of placebo-treated (i.e. control) animals, had, on average, a higher necrotic fraction than control tumours. Thus, it is concluded that zilascorb(2H) induces tumour necrotisation and not just inhibition of the rate of tumour cell production. Continued measurement of tumour volume after ended treatment with zilascorb(2H) indicated that surviving tumour cells resumed their normal growth rate immediately. The reversibility of the effect induced by this compound, earlier observed in vitro only, is therefore here confirmed to be valid also in two different tumour xenografts in vivo. The present data accords well with the assumption that protein synthesis inhibition is the primary cellular effect of zilascorb(2H) in vivo. We therefore conclude that zilascorb(2H)-induced cancer cell lethality in tumour xenografts probably comes as a secondary consequence of prolonged protein synthesis inhibition.

Report this publication

Statistics

Seen <100 times