Biological Activity

Bleomycin sulfate (Blenoxane) is an anticancer agent for squamous cell carcinomas with IC50 of 4 nM in UT-SCC-19A cells. Bleomycin sulfate inhibits DNA synthesis and causes DNA scissions at specific base sequences. Bleomycin sulfate also inhibits tumor angiogenesis. Bleomycin sulfate causes single and double-strand DNA breaks in tumor cells, which interrupts the cell cycle. Bleomycin is thought to achieve this by chelating metal ions, producing a pseudoenzyme that reacts with oxygen to produce superoxide and hydroxide free radicals that cleave DNA. Bleomycin sulfate-induced telomere instability in mammalian cells persists for several generations after exposure. Moreover, the appearance of telomere fusions in Bleomycin sulfate-exposed cells 10 days after treatment suggests that Bleomycin sulfate can induce delayed telomere instability.

Product Citations

• 

  Adv Biol (Weinh). 2023 Feb 12;e2200265.

  COVID‐19 Metabolomic‐Guided Amino Acid Therapy Protects from Inflammation and Disease Sequelae
  Bleomycin sulfate purchased from AbMole

• 

  research square. 2022 July 11.

  Neutrophil-driven CD206hiMHCIIlo macrophages are critical for skin fibrosis during systemic sclerosis
  Bleomycin sulfate purchased from AbMole

• 

  Cell Death Discov. 2022 Nov 26;8(1):466.

  Mesenchymal stem cells alleviate systemic sclerosis by inhibiting the recruitment of pathogenic macrophages
  Bleomycin sulfate purchased from AbMole

Protocol (for reference only)

Cell Experiment
Cell lines	MIA PaCa-2 cell
Preparation method	Proliferation assay. The effect of EGCG and BLM on cell proliferation was determined by using TACS 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay (Trevigen, Githersburg). The cells (2000 per well) were incubated with EGCG alone, BLM alone or combination of EGCG and BLM, in triplicate in a 96-well plate and then incubated for 2, 4 and 6 days at 37 °C. A MTT solution was added to each well and incubated for 2 h at 37 °C. An extraction buffer (20 % SDS and 50 % dimethylformamide) was added, and the cells were incubated overnight at 37 °C. The absorbance of the cell suspension was measured at 570 nm using a microplate reader (DAS Technologies, Chantilly, VA). This experiment was repeated twice, and the statistical analysis was performed to obtain the final values.
Concentrations	0, 10 and 20 μM
Incubation time	2, 4 and 6 days

Animal Experiment
Animal models
Formulation
Dosages
Administration

Chemical Information

Molecular Weight	1512.62
Formula	C55H85N17O25S4
CAS Number	9041-93-4
Solubility (25°C)	Water ≥ 80 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Bimonte S, et al. Infect Agent Cancer. Inhibitory effect of (-)-epigallocatechin-3-gallate and bleomycin on human pancreatic cancer MiaPaca-2 cell growth.

[2] Huang LS, et al. FASEB J. Targeting sphingosine kinase 1 attenuates bleomycin-induced pulmonary fibrosis.

[3] Banerjee ER, et al. Stem Cell Res Ther. Characterization of lung stem cell niches in a mouse model of bleomycin-induced fibrosis.

[4] Danesi CC, et al. Mutat Res. Genotoxicity testing of combined treatment with cisplatin, bleomycin, and 5-fluorouracil in somatic cells of Drosophila melanogaster.

[5] Paviolo NS, et al. Mutat Res. Telomere instability is present in the progeny of mammalian cells exposed to bleomycin.