Bleomycin

9041-93-4 (Bleomycin Complex)

C55H84N17O21S3 (for A2)

1415.6 (Bleomycin A2)

Off-white solid

Bleomycin is soluble in water and methanol, with moderate ethanol solubility.

-20°C

Cancer Applications: Bleomycin contains a disaccharide moiety composed of 2 unusual sugars, L-glucose and 3-O-carbamoyl-D-mannose. Bleomycin could be regarded as a modular system composed of a tumor-targeting agent (the dissacharide moiety) and a tumoricidal agent (deglycobleomycin). The disaccharide moiety is responsible for the tumor cell targeting properties of Bleomycin. Bleomycin analogs were prepared, the glycosylated analogs were more cytotoxic to cultured DU145 prostate cancer cells. These findings establish a role for the Bleomycin disaccharide in tumor targeting/uptake and suggest that the disaccharide moiety may be capable of delivering other cytotoxins to cancer cells. Cytotoxicity testing with DU145 human prostate cancer cells in vitro (Schroeder et al, 2014).
Bleomycin is used in combination with other antineoplastic agents in studying lymphomas, testicular carcinomas, and squamous cell carcinomas. Authors found that the human L-carnitine transporter (hCT2) is involved in bleomycin-A5 uptake. NT2/D1 human testicular cancer cells which highly express hCT2 are very sensitive to Bleomycin-A5. Data suggest that hCT2 can mediate the uptake of Bleomycin A5 (Aouida et al, 2010).
In cell culture experiments with Bleomycins and BLM carbohydrates conjugated to microbubbles, it has been demonstrated that Bleomycins are tumor-seeking molecules. Biotinylate Bleomycin A5 was attached to microbubbles, and a conjugate-containing solution was passed over a monolayer of MCF-7 cells. The microbubbles adhered to the MCF-7 cells. The conjugate did not bind to a normal breast cell line or to matched noncancer cell lines. No binding occurred if the microbubbles lacked conjugated Bleomycin A5 or if the microbubble lacked the carbohydrate moiety (Chapuis et al, 2009).
A well-known characteristic of tumor cells is the Warburg effect, that is the propensity of tumor cells to produce increased ATP via glycolysis rather than by mitochondrial oxidative phosphorylation. The shift to glycolysis is accompanied by upregulation of glucose transporters to provide the greater amounts of glucose needed to support increased glycolysis. If authors treated two normal cell lines (normal WI-38 cells and normal kidney CCD-1105 KIDTr cells) with the inhibitor rotenone (a mitochondrial complex 1 inhibitor), this forced these cells to use increase glycolysis in the same fashion as tumor cells and this resulted in an enhanced ability to incorporate BLM-Cy5. The finding implies that the BLM saccharide moiety may be able to deliver other cytotoxins selectively to tumor cells (Mobasheril, 2005).