Siomycin is a macrocyclic thiopeptide antibiotic with potent and selective antibacterial activity first isolated from the fermentation product of Streptomyces sioyaensis by Nishimura in 1959. This member of the thiostrepton family is a potent inhibitor of the oncogenic transcription factor, FoxM1. In vitro, siomycin inhibits FoxM1-induced cell growth on soft agar and selectively kills transformed cells. Siomycin has anti-cancer properties.
Siomycin is soluble in DMF and DMSO.
|Mechanism of Action||Siomycin inhibits protein synthesis in bacteria by interfering with rRNA binding, specifically the 23S rRNA. The reduction in transcription activity is reflected in the down-regulation of protein and mRNA levels of the transcription factor Forkhead box family ( FoxM1) and effects on downstream genes, Cdc25B, survivin and CENPB.|
|Cancer Research Applications||
The antitumor effects of Siomycin A in vitro was studied and was shown to inhibit proliferative ability a variety of human tumor cell lines. it also affected the cytoskeleton of tumor cells by downregulating the expression of a-tubulin protein (ref). Cell viabilitly was reduced with increased Siomycin concentration, for a dose-dependent effect (Wang et al, 2019).
Siomycin A induces reactive oxygen species-mediated cytotoxicity in ovarian cancer cells PA1 and OVCAR3 and inhibited proliferation of ovarian cancer cells (Shao et al, 2020).
FOXM1 is a key transcription factor regulating oncogenic signaling pathways in meningioma (Kim et al, 2020).
Ebata M et al (1969) Studies on Siomycin. I Physicochemical properties of Siomycin A, B and C. J. Antibiot Ser. A, 22:364
Kim H et al (2020) Forkhead box M1 (FOXM1) transcription factor is a key oncogenic driver of aggressive human meningioma progression. Neuropathol Appl. Neurobiol. 46(2):125-141
Miyazaki K, Ebata M and Otsuka H (1969) Studies on Siomycin III. J. Antibiotics 22(9):434-441 PMID 4899606
Radhakrishnan et al (2006) Identification of a chemical inhibitor of the oncogenic transcription factor Forkhead Box M1. Cancer Res. 19: 9731
Shao X, Zhang F, Gao X, Xu F (2021) Siomycin A induces reactive oxygen species-mediated cytotoxicity in ovarian cancer cells. Oncol Lett.;21(6):431 PMID 33868469
Wang B, Wang W, Meng HY, Chen J, Yuan LJ (2019) Effects and mechanism of Siomycin A on the growth and apoptosis of MiaPaCa-2 cancer cells. Oncol Lett. 18(3):2869-2876 PMID 31452766