| Autor: |
Martins de Oliveira L; Department of General Biology, Center of Biological Sciences, Londrina State University, UEL, Londrina, Brazil., Alves de Lima LV; Department of General Biology, Center of Biological Sciences, Londrina State University, UEL, Londrina, Brazil., Silva MFD; Department of General Biology, Center of Biological Sciences, Londrina State University, UEL, Londrina, Brazil., Felicidade I; Department of General Biology, Center of Biological Sciences, Londrina State University, UEL, Londrina, Brazil., Lepri SR; Department of General Biology, Center of Biological Sciences, Londrina State University, UEL, Londrina, Brazil., Mantovani MS; Department of General Biology, Center of Biological Sciences, Londrina State University, UEL, Londrina, Brazil. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of toxicology and environmental health. Part A [J Toxicol Environ Health A] 2023 Nov 17; Vol. 86 (22), pp. 859-870. Date of Electronic Publication: 2023 Sep 06. |
| DOI: |
10.1080/15287394.2023.2255886 |
| Abstrakt: |
Curcumin is an antiproliferative phytochemical extracted from Curcuma longa L and which has been studied in preclinical drug screening using cell monolayers and animal models. However, several limitations of these culture systems may be overcome by performing screening with three-dimensional (3-D) cell culture. The aim of this study was to investigate the effects of curcumin on cytotoxicity and genotoxicity as well as spheroid growth using cervical adenocarcinoma HeLa cell spheroids by performing RT-PCR mRNA expression of genes involved in cell death ( CASP3 , CASP8 , CASP9 , PARP1 , BBC3 , BIRC5 , BCL2 , TNF ), autophagy ( BECN1, SQSTM1 ), cell cycle regulation ( TP53 , C-MYC , NF-kB , CDKN1A , m-TOR , TRAF-2 ), DNA damage repair ( H2AFX , GADD45A, GADD45G ), oxidative stress ( GPX1 ), reticulum stress ( EIF2AK3, ERN1 ), and invasion ( MMP1 , MMP9 ) was investigated. Curcumin was cytotoxic in a concentration-dependent manner. Curcumin-treated spheroids exhibited lower proliferative recovery and cell proliferation attenuation, as observed in the clonogenic assay. Further, no marked genotoxicity was detected. Curcumin-treated spheroids displayed reduced expression of BECN1 (2.9×), CASP9 (2.1×), and PARP1 (2.1×) mRNA. PARP1 inhibition suggested disruption of essential pathways of proliferation maintenance. Downregulated expression of CASP9 mRNA and unchanged expression of CASP3/8 mRNA suggested caspase-independent cell death, whereas downregulated expression of BECN1 mRNA indicated autophagic disruption. Therefore, curcumin exhibits the potential for drug development with antiproliferative activity to be considered for use in cancers. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
