RESUMEN
Polo-like kinase 1 (PLK1) is crucial in regulating cell division and has been shown to have an oncogenic function in several cancers. Since PLK1 overexpression is closely related to tumorigenesis and has been correlated with poor clinical outcomes, specific inhibition of PLK1 in cancer cells is a promising approach for developing new anticancer drugs. In this context, the aim of the present study was to evaluated the potential cytotoxic effects of GSK461364A, a competitive inhibitor for PLK1, in gastric cancer cell line SNU-1 cells and explored its cytotoxic mechanism. The cells were exposed to GSK461364A at different concentrations ranging from 1 to 40 µM for 24 h, and it showed considerable cytotoxicity with an IC50 value of 4.34 µM. The treatment of SNU-1 cells with GSK461364A results in cell cycle arrest at the G2/M phase, decreased mitochondrial membrane potential, and increased apoptosis as indicated by Annexin V binding assay. In addition, GSK461364A treatment significantly increased the total oxidant (TOS) level, a signal of oxidative stress, and increased cleaved PARP and 8-oxo-dG levels as an indicator of DNA damage. ELISA experiments evaluating Bax, BCL-2, and cleaved caspase 3 also confirmed the apoptotic effect of GSK461364A. Current findings suggest that GSK461364A may be a chemotherapeutic agent in patients with gastric cancer. Nevertheless, more research is needed to evaluate GSK461364A as a cancer treatment drug.
Asunto(s)
Antineoplásicos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Proteínas de Ciclo Celular/genética , Puntos de Control del Ciclo Celular , Apoptosis , Antineoplásicos/farmacología , Proliferación Celular , Línea Celular TumoralRESUMEN
An inverse association between serum lycopene levels and the risk of cancers has been pointed out by many prospective and retrospective epidemiological studies which prompted more studies to be performed on animal models and cell cultures in order to test this hypothesis. The aim of the present study was to evaluate the antiproliferative and pro-apoptotic effect of lycopene on colon cancer HT-29 cell line. The effect of lycopene on the viability of HT-29 cell line was investigated using XTT assay. The levels of Bcl-2, cleaved caspase 3, BAX, cleaved PARP, and 8-oxo-dG in lycopene-treated HT-29 cells were measured using ELISA. Gamma-H2AX and cytochrome c expression was assessed semi-quantitatively using immunofluorescence staining. Lycopene at doses of 10 and 20 µM produced a significant antiproliferative effect on HT-29 cells compared to the control (p < 0.05). The IC50 value of lycopene in HT-29 cells was found to be 7.89 µM for 24 h. Lycopene (7.89 µM) significantly elevated cleaved caspase 3 (p < 0.01), BAX, and cleaved PARP, 8-oxo-dG levels (p < 0.05). The levels of γ-H2AX foci are significantly higher while the levels of cytochrome-c are lower (p < 0.05) in lycopene-treated HT-29 cells. These results indicate that lycopene has an antiproliferative apoptotic and genotoxic effect on HT-29 colon cancer cell line.