Kazusamycin B is a metabolite and minor member of the Leptomycin complex isolated from some Streptomyces species. It is a hydroxylated analog of Leptomycin A, a nuclear export inhibitor. It is similar to Leptomycins A and B in physico-chemical and biological characteristics. It has anti-cancer properties. This metabolite can inhibit nuclear export and translocation of Rev, a gene product in the HIV-1 genome, at nanomolar concentrations.
Kazusamycin B is soluble in ethanol and methanol but is practically insoluble in water. It is unstable in DMSO.
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| Mehanism of Action |
Members of the Leptomycin complex can induce abnormal condensation of nuclei and arrest cell cycle of yeast and mammalian cells in both G1 and G2 phases, but the mechanism of action is still unknown. |
| Microbiology Applications | Kazusamycin A and B, along with Leptomycins A and B were isolated from Streptomyces sp. strain A87-18203. These compounds were identified via a screening assay for low MW inhibitors of Rev nuclear transport. They were all found to inhibit the translocation of the regulatory protein Rev at nanomolar concentrations. Rev is need for viral replication of HIV-1 (Wolff et al, 1997). |
| Cancer Applications | Kazusamycin B has potent antitumor activity against L1210 cells, arresting the cell cycle at the G1 phase (Takamiya et al, 1988). It also has activity against experimental tumors including murine tumors S180, EL-4, and B16. It had in vitro against doxorubicin-resistant P388 cells (Yoshida et al, 1987). It had cytocidal activity against P388 leukemia cells in vitro (Funaishi et al, 1987). |
| Eukaryotic Cell Culture Applications | Kazusamycin A has strong cytotoxic activity against HeLa cells in vitro, and when used at 3.3 ng/ml, it prevented cell growth (Umezawa et al, 1984). |
| References |
Funaishi K et al (1987) Kazusamycin B, a novel antitumor antibitioc. J. Antibiot. (Tokyo) 40(6):778-785 Hurley TR et al (1986) PD 124,895 and PD 124,966, two new antitumor antibiotics. J. Antibiot. 39:1651 Komiyama K et al (1985) Antitumor activity of a new antibiotic, Kazusamycin. J. Antibiot. 38:224 Roberts BJ et al (1986) In vivo and in vitro anticancer activity of the structurally novel and highly potent antibiotic CI-940 and its hydroxy analog (PD 114,721). Cancer. Chemother. Pharmacol. 16:95 Sawamura M (1992) Growth inhibitory effect of a new anticancer antibiotics, Kazusamycin A, on human transitional cancer cell lines in vitro. Nihon Hinyokika Gakkai Zasshi. 83(5):627-635 PMID 1495200 Takamiya K(1988) The effect of Kazusamycin B on the cell cycle and morphology of cultured L1210 cells. J. Antibiot. (Tokyo) 41(12):1854-1861 PMID 3209477 Umezawa I et al (1984) A new antitumor antibiotic, Kazusamycin. J. Antibiot. (Tokyo) 37(7):706-711 PMID 6432763 Wolff B et al (1997) Leptomycin B is an inhibitor of nuclear export: Inhibition of nucleo-cytoplasmic translocation of the human immunodeficiency virus type 1 (HIV-1) Rev protein and Rev-dependent mRNA. Chem. Biol. 4:139 PMID 9190288 Yoshida et al (1987) Antitumor effect of Kazusamycin B on experimental tumors. J. Antibiot. (Tokyo) 40(11):1596-1604 PMID 3693127 |
