Verrucarin A

Verrucarin A (Muconomycin A), a Type D macrocyclic mycotoxin derived from the pathogen fungus Myrothecium verrucaria, is an inhibitor of protein synthesis. Verrucarin A inhibits growth of leukemia cell lines and activates caspases and apoptosis and inflammatory signaling in macrophages. VA effectively increased the phosphorylation of p38 MAPK and diminished the phosphorylation of ERK/Akt. VA caused cell cycle deregulation through the induction of p21 and p53[1][2].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Verrucarin A (0-0.6 μM/ml; 24-48 hours)-induces time- and dose-dependent growth inhibition in MCF-7 cells[1]. Verrucarin A increases the levels of reactive oxygen species (ROS), and subsequently induces mitochondrial membrane potential (Δψm) loss, leading to the increase of Bax/Bcl-2 ratio, cytochrome c release, caspase activation, PARP degradation, and apoptosis[1]. Cell Viability Assay[1] Cell Line: MCF-7 cells Concentration: 0-0.6 μM/ml Incubation Time: 24 and 48 hours Result: Growth of MCF-7 cells is significantly inhibited in a dose- and time-dependent manner, with the IC50s of 0.41 and 0.29 μM/ml for 24- and 48-h treatment periods, respectively.

[1]. Palanivel K, et al. Verrucarin A alters cell-cycle regulatory proteins and induces apoptosis through reactive oxygen species-dependent p38MAPK activation in the human breast cancer cell line MCF-7. Tumour Biol. 2014;35(10):10159-10167.

[2]. Palanivel K, et al. Verrucarin A, a protein synthesis inhibitor, induces growth inhibition and apoptosis in breast cancer cell lines MDA-MB-231 and T47D. Biotechnol Lett. 2013;35(9):1395-1403.

MOLECULAR FORMULA :

C27-H34-O9

MOLECULAR WEIGHT :

502.61

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

Standard Draize test

ROUTE OF EXPOSURE :

Administration onto the skin

SPECIES OBSERVED :

Rodent - guinea pig

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

870 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

500 ug/kg

TOXIC EFFECTS :

Skin and Appendages - dermatitis, other (after systemic exposure) Biochemical - Metabolism (Intermediary) - effect on inflammation or mediation of inflammation

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

3900 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1500 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

540 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

14 mg/kg/8W-C

TOXIC EFFECTS :

Blood - changes in leukocyte (WBC) count

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Primate - monkey

DOSE/DURATION :

5 mg/kg/50D-C

TOXIC EFFECTS :

Blood - leukopenia Blood - changes in cell count (unspecified) Related to Chronic Data - death

MUTATION DATA

TYPE OF TEST :

DNA inhibition

TEST SYSTEM :

Rodent - mouse Lymphocyte

DOSE/DURATION :

1 nmol/L

REFERENCE :

PLMEAA Planta Medica. (Georg Thieme Verlag, Postfach 732, D-7000 Stuttgart 1, Fed. Rep. Ger.) V.1- 1953- Volume(issue)/page/year: 34,231,1978