RESUMO
Benzo[ghi]perylene is the most abundant polycyclic aromatic hydrocarbon in the atmosphere of highly polluted cities with high altitudes like Mexico City. We evaluated the in vitro cytotoxic and genotoxic effects that Benzo[ghi]perylene could induce to the bronchial cell line NL-20 after 3â¯h of exposure. Furthermore, exposed cells were washed and maintained for 24â¯h without the treatment (recovery time), in order to evaluate a persistent damage to the cells. We found that at 3â¯h of exposure, 20% and 47% of the cells displayed cytoplasmic vesicles (pâ¯<0.05) and É£H2AX foci in the nuclei (pâ¯<0.05), respectively. Furthermore, 27% of cells showed translocation of the factor inductor apoptosis into the nuclei (pâ¯<0.05) and an increase of proliferating cells was also observed (21%, pâ¯<0.05). The cells after recovery time continued displaying morphological changes and É£H2AX foci, despite of the increased expression (> 2-times fold change) of some DNA repair genes (pâ¯<0.05) found before the recovery time. We also found that the cell nuclei contained Benzo[ghi]perylene after the exposure and it remains there after the recovery time (pâ¯<0.01). Therefore, hereby we report the cytotoxic and genotoxic effects that Benzo[ghi]perylene is capable to induce to NL-20 cells.
Assuntos
Poluentes Atmosféricos/toxicidade , Dano ao DNA , Perileno/análogos & derivados , Apoptose/efeitos dos fármacos , Brônquios/citologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Histonas/metabolismo , Humanos , Perileno/toxicidadeRESUMO
Curcumin is a polyphenol compound extracted from Curcuma longa plant, is a molecule with pleiotropic effects that suppresses transformation, proliferation and metastasis of malignant tumors. Curcumin can cause different kinds of cell death depending of its concentration on the exposed cell type. Here we show that exposure of the glioblastoma cell line A172 to curcumin at 50⯵M, the IC50, causes morphological change characteristic of paraptosis cell-death. Vesicles derived from the endoplasmic reticulum (ER) and low membrane potential of the mitochondria were constantly found in the exposed cells. Furthermore, changes in expression of the ER Stress Response (ERSR) genes IRE1 and ATF6, and the microRNAs (miRNAs) miR-27a, miR-222, miR-449 was observed after exposure to curcumin. AKT-Insulin and p53-BCL2 networks were predicted being modulated by the affected miRNAs. Furthermore, AKT protein levels reduction was confirmed. Our data, strongly suggest that curcumin exerts its cell-death properties by affecting the integrity of the reticulum, leading to paraptosis in the glioblastoma cells. These data unveils the versatility of curcumin to control cancer progression.