Deoxynybomycin is a selective anti-tumor agent inducing apoptosis and inhibiting topoisomerase I

Citation
K. Egawa et al., Deoxynybomycin is a selective anti-tumor agent inducing apoptosis and inhibiting topoisomerase I, BIOL PHAR B, 23(9), 2000, pp. 1036-1040
Citations number
24
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOLOGICAL & PHARMACEUTICAL BULLETIN
ISSN journal
0918-6158 → ACNP
Volume
23
Issue
9
Year of publication
2000
Pages
1036 - 1040
Database
ISI
SICI code
0918-6158(200009)23:9<1036:DIASAA>2.0.ZU;2-T
Abstract
Deoxynybomycin was identified as an inducer of p21the/WAF1 gene following s creening using a reporter, p21/luciferase, The present study examined its a nti-proliferative effect on human tumor cell lines. Deoxynybomycin selectiv ely inhibited growth of human osteoblastic sarcoma Saos-2, gastric cancer T MK-1, and monocytic leukemia THP-1 cells, but did not affect survival of no rmal human fibroblasts at doses up to 5 mu g/ml. Results from an assay syst em using a panel of 39 human cancer cell lines indicated that deoxynybomyci n has selective cytotoxic activity against lung carcinoma cell lines. Deoxy nybomycin induced apoptosis in Saos-2, TMK-1, and THP-1 cells as revealed b y DNA fragmentation and TUNEL assays. It inhibited topoisomerase I but not topoisomerase II. These results suggest that deoxynybomycin may be useful i n cancer chemotherapy.