The pesticide malathion induces alterations in actin cytoskeleton and in cell adhesion of cultured breast carcinoma cells.
We have studied the effects of the organophosphorous pesticide malathion on cell viability, actin cytoskeleton, cell adhesion complex E-cadherin/beta-catenin, and Rho and Rac1 GTPases from the human mammary carcinoma cell line MCF-7. Malathion induced cell lethality, determined by the MTT assay, depending on the treatment conditions. Cells incubated with low concentrations of malathion, 16-32 microg/ml, showed high survival rates (>95%) at any evaluated time (1-5 days), whereas complete cell lethality was found using 512 microg/ml and 5 days of treatment. Deep morphological changes were induced with high doses of 64 and 128 microg/ml, and long incubation time (5 days); cells showed perinuclear vacuoles, rounding, shrinkage, and a gradual loss of adhesion. These changes were related to a decrease in the expression of the adhesion molecules, E-cadherin and beta-catenin, and to the distribution and reactivity of actin microfilaments to TRITC-phalloidin. Disruption of microfilaments, accompanied by the collapse of actin to perinuclear region, were characteristic of cells with loss of adhesion. At lower concentrations, some cells presented deformations on the plasma membrane as lamellipodia-like structures, which were particularly evident from 32 to 128 microg/ml. Conversely, we observed an increase in the expression of Rho and Rac1 GTPases, modulators of actin cytoskeleton and cell adhesion.
Cabello
G
G
Centro de Investigaciones del Hombre en el Desierto, Facultad de Ciencias, Departamento de Biología y Salud, Universidad de Tarapacá, Arica, Chile.
Galaz
S
S
Botella
L
L
Calaf
G
G
Pacheco
M
M
Stockert
J C
JC
Villanueva
A
A
Cañete
M
M
Juarranz
A
A
D000199:Actins / Q000737:chemistry* / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy*; D015820:Cadherins / Q000096:biosynthesis; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004396:Coloring Agents / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D004586:Electrophoresis; D006801:Humans; D007306:Insecticides / Q000494:pharmacology; D008294:Malathion / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D015534:Trans-Activators / Q000096:biosynthesis; D051176:beta Catenin; D020830:rac1 GTP-Binding Protein / Q000096:biosynthesis; D020741:rho GTP-Binding Proteins / Q000096:biosynthesis
D000199:Actins; C495270:CTNNB1 protein, human; D015820:Cadherins; D002800:Cholinesterase Inhibitors; D004396:Coloring Agents; D003598:Cytoskeletal Proteins; D007306:Insecticides; D013778:Tetrazolium Salts; D013844:Thiazoles; D015534:Trans-Activators; D051176:beta Catenin; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; C022616:thiazolyl blue; D008294:Malathion