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

Abstract

Deoxynybomycin was identified as an inducer of p21the/WAF1 gene following screening using a reporter, p21/luciferase. The present study examined its anti-proliferative effect on human tumor cell lines. Deoxynybomycin selectively inhibited growth of human osteoblastic sarcoma Saos-2, gastric cancer TMK-1, and monocytic leukemia THP-1 cells, but did not affect survival of normal human fibroblasts at doses up to 5 microg/ml. Results from an assay system using a panel of 39 human cancer cell lines indicated that deoxynybomycin has selective cytotoxic activity against lung carcinoma cell lines. Deoxynybomycin induced apoptosis in Saos-2, TMK-1, and THP-1 cells as revealed by DNA fragmentation and TUNEL assays. It inhibited topoisomerase I but not topoisomerase II. These results suggest that deoxynybomycin may be useful in cancer chemotherapy.

• Authors: K Egawa, T Yamori, C Nosaka, S Kunimoto, T Takeuchi, K Nos
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 23 Issue 9 Pg. 1036-40 (Sep 2000) ISSN: 0918-6158 [Print] Japan
• PMID: 10993200 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• Cyclins
• Enzyme Inhibitors
• Quinolones
• Topoisomerase I Inhibitors
• deoxynybomycin

Topics

• Antibiotics, Antineoplastic (pharmacology)
• Apoptosis (drug effects)
• Cyclin-Dependent Kinase Inhibitor p21
• Cyclins (genetics)
• Enzyme Inhibitors (pharmacology)
• Humans
• Promoter Regions, Genetic
• Quinolones (pharmacology)
• Topoisomerase I Inhibitors
• Tumor Cells, Cultured