Bleomycin is a complex of 11 glycopeptide antibiotics originally isolated from Streptomyces verticillus in 1972. The dominant components are Bleomycin A2 and Bleomycin B2, which typically represent >90% of the total weight. Bleomycin has anti-cancer properties.
We also offer:
- Bleomycin Sulfate, USP (B005)
- Bleomycin A2 Sulfate (B019)
- Bleomycin A5 Hydrochloride (B004)
- Demethylbleomycin A2 Sulfate, EvoPure® (D023)
|Mechanism of Action||Bleomycins act by intercalation of DNA and RNA. In the presence of oxygen and metal ions, notably copper and iron, Bleomycins form a pseudo-enzyme that induces DNA cleavage. Bleomycin's anticancer activities include the increase of caspase-3 and p53, and the inhibition of telomerase activity leading to apoptosis. The anti-cancer properties derives from its ability to effect DNA cleavage in cancer cells.|
|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).
|Molecular Formula||C55H84N17O21S3 (for A2)|
|Solubility||Bleomycin is soluble in water and methanol, with moderate ethanol solubility.|
Aouida M, Poulin P and Ramotar (2010) The human carnitine transporter SLC22A16 mediates high affinity uptake of the anticancer polyamine analogue Bleomycin-A5. J. Biol. Chem. 285:6275-6284Burger RM, Paisach J, and Horwitz SB (1981) Mechanism of Bleomycin action: In vitro studies. Life Sci. 28(7):715-727 PMID 6164898
Chapuis J, Schmaltz RM, Tsosie KS, Belohlavek M and Hecht SM (2009) Carbohydrate dependent targeting of cancer cells by Bleomycin-microbubble conjugates. J. Am. Chem. Soc. 131(7):2438-2439Dorr, RT (1991) Bleomycin Pharmacology: Mechanism of action and resistance, and clinical pharmacokinetics. Semin. Oncol. 19(2): 3-8 PMID 1384141
Fujiwara Y and Kondo T (1973) Strand-scission of HeLa cell deoxyribonucleic acid by Bleomycin in vitro and in vivo. Biochem. Pharmacol 22(3):323-333 PMID 4119868
Kross et al (1982) Structural basis for the deoxyribonucleic acid affinity of Bleomycins. Biochem. 21: 3711-3721 PMID 6180763
Kross et al (1982) Specificity of deoxyribonucleic acid cleavage by Bleomycin, phleomycin and tallysomycin. Biochem. 21:4310 PMID 6181807
Mobasheril, A, Richardson S, Mobasheri R, Shakibaei M, Hoyland, J (2005) Hypoxia inducible factor-1 and facilitative glucose transporters GLUT1 and GLUT3: Putative molecular components of the oxygen and glucose sensing apparatus in articular chondrocytes. Histol. Histopathol. 20(4):1327-1338 PMID 16136514Mulsant P, Gatignol A, Dalens M and Tiraby, G (1988) Phleomycin resistance as a dominant selectable marker in CHO cells. Som. Cell and Mol. Gen. 14(3):243–252 PMID: 2453083
Schroeder BR et al (2014) The disaccharide moiety of Bleomycin facilitates uptake by cancer cells. J. Am. Chem Soc. 136(39):13641-13656Takita T et al (1972) Chemistry of Bleomycin. IX. The structures of Bleomycin and phleomycin. J. Antibiot. (Tokyo) 25:755-757 PMID 4119701
Yang L, Yang S, Tai K, Chou M and Yang J (2004) MEK inhibition enhances Bleomycin A5-induced apoptosis in an oral cancer cell line: Signaling mechanisms and therapeutic opportunities. J. Oral Path. and Med. 33(1):37-45