Deoxynybomycin is a selective anti-tumor agent inducing apoptosis and inhibiting topoisomerase I.
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.
Egawa
K
K
Microbial Chemistry, Kamiosaki, Tokyo, Japan.
Yamori
T
T
Nosaka
C
C
Kunimoto
S
S
Takeuchi
T
T
Nos
K
K
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D011401:Promoter Regions, Genetic; D015363:Quinolones / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D015363:Quinolones; D059004:Topoisomerase I Inhibitors; C000874:deoxynybomycin