RESUMEN
Icariin has been reported to possess high anticancer activity. Colon carcinoma is one of the leading causes of cancer-related mortality worldwide. Here, the anticancer activity of icariin against HCT116 colon carcinoma cells and the possible underlying mechanism were studied. The trypan blue staining assay, wound healing assay, clonogenic assay, CCK-8 assay, and Annexin V-FITC/PI double staining method were carried out to determine the changes of HCT116 cell growth and migration. mRNA and protein expressions were determined by quantitative real-time PCR and western blot, respectively. Moreover, small interfering RNA (siRNA) plasmid was used to examine the role of p53 in icariin-induced apoptosis in HCT116 cells. Icariin significantly suppressed colon carcinoma HCT116 cells by decreasing migration and viability, and simultaneously promoting apoptosis. Icariin exerted the anti-tumor effect in a dose-dependent manner by up-regulating p53. During treatment of icariin, p-p53, p21, and Bax levels increased, and Bcl-2 level decreased. Short time treatment with icariin induced DNA damage in HCT116 cells. Furthermore, the cytotoxicity of icariin was decreased after p53 knockdown or by using caspase inhibitors. p53 was involved in activities of caspase-9 and caspase-3. Icariin repressed colon carcinoma cell line HCT116 by enhancing p53 expression and activating p53 functions possibly through Bcl-2/Bax imbalance and caspase-9 and -3 regulation. Icariin treatment also induced DNA damage in HCT116 cells.
Asunto(s)
Humanos , Flavonoides/farmacología , Movimiento Celular/efectos de los fármacos , Proteína p53 Supresora de Tumor/efectos de los fármacos , Apoptosis/efectos de los fármacos , Neoplasias del Colon/patología , Proliferación Celular/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Western Blotting , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias del Colon/metabolismo , ARN Interferente Pequeño , Células HCT116 , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
The gastrointestinal tract (GIT) is exposed to various environmental pollutants including metals, that contaminate food and water which may have toxic effects on body. GIT has large amount of microbes that live in symbiosis and help the host in different ways. The resident gut microflora have a significant role to play in detoxification and elimination of the harmful metals from the body. Chromium is a naturally occurring heavy metal found commonly in environment in trivalent (Cr III) and hexavalent (Cr VI) forms. Cr (VI) compounds have been shown to be potent occupational carcinogens. The reduction of Cr (VI) to Cr (III) results in the formation of reactive intermediates that together with oxidative stress and oxidative tissue damage, and a cascade of cellular events including modulation of apoptosis regulatory gene p53 contribute to the cytotoxicity, genotoxicity and carcinogenicity of Cr(VI)-containing compounds. The data discussed here with reference to chromium show that gut microflora have a marked capacity to cope with the increased load of ingested metals and may contribute significantly in the protection against metal toxicity.