Boromycin abrogates bleomycin-induced G2 checkpoint.

Abstract

The DNA-damaging agent bleomycin arrests the cell cycle at the G2 phase of Jurkat cells defective in the G1 checkpoint, and microtubule-acting colchicine arrests it at the M phase. Boromycin itself, an actinomycete metabolite, showed no effect on the cell cycle status of Jurkat cells at least up to 340 nM. However, the compound (3.4-340 nM) was found to abrogate bleomycin-induced G2 arrest even at 3.4 nM, resulting in a drastic decrease in cells at the G2 phase and increase in cells at the subG1 phase. On the other hand, boromycin did not show any effect on the colchicine-induced M phase arrest in Jurkat cells, nor on the cell cycle status of the bleomycin-treated or -untreated HUVEC, normal cells conserving both G1 and G2 checkpoints. Furthermore, boromycin potentiated anti-tumor activity of bleomycin in scid mice inoculated with Jurkat cells. These data suggest that boromycin disrupts the cell cycle at the G2 checkpoint of cancer cells selectively, leading to sensitization of cancer cells to anti-cancer reagents.

• Authors: Masayoshi Arai, Yukio Koizumi, Hitoshi Sato, Takumi Kawabe, Masashi Suganuma, Hidetaka Kobayashi, Hiroshi Tomoda, Satoshi Omura
• Journal: The Journal of antibiotics (J Antibiot (Tokyo)) Vol. 57 Issue 10 Pg. 662-8 (Oct 2004) ISSN: 0021-8820 [Print] England
• PMID: 15638327 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Borates
• Bleomycin
• boromycin

Topics

• Animals
• Bleomycin (pharmacology)
• Borates (pharmacology)
• G2 Phase (drug effects)
• Humans
• Jurkat Cells
• Male
• Mice
• Mice, SCID