RESUMEN
PURPOSE: Xanthohumol is a prenylated flavonoid of plant origin and has been reported to exhibit a spectrum of pharmacological properties including anticancer effects. However, the anticancer properties of Xanthohumol have not been thoroughly evaluated against drug-resistant colon cancer cells. This study was undertaken to evaluate the anticancer effects of Xanthohumol against the human colon cancer cell line HT-29 and normal CDD-18Co cell line. METHODS: HT-29 cell viability was evaluated by cell counting kit-8 (CCK8) assay. Apoptotic effects were examined by fluorescence microscopy using DAPI staining and flow cytometry using annexin V/propidium iodide (PI) staining. Effects on cell cycle were studied by flow cytometry while western blot analysis was done to study effects on protein expressions. RESULTS: The results showed that Xanthohumol causes a dramatic decrease in the HT-29 cell viability with an IC50 of 10 µM. However, an IC50 >100 µM for Xanthohumol against the normal CDD-18Co cells suggested cancer cell specific activity. DAPI staining revealed nuclear fragmentation, suggesting xanthohumol induces apoptosis in HT-29 cells. Xanthohumol also caused activation of caspase-3 and 9 and increased the Bax/Bcl-2 ratio. Cell cycle analysis showed that this molecule caused arrest of the HT-29 cells at the G2/M phase of the cell cycle. The induction of G2/M cell cycle was also accompanied with depletion of the expression of cyclin B1. The effects of Xanthohumol were also investigated on the Ras/MEK/ERK signalling pathway which revealed that Xanthohumol also blocks the MEK/ERK signalling pathway in colon cancer cells in a concentration-dependent manner. CONCLUSIONS: Xanthohumol may prove an efficient lead molecule for the development of more potent anticancer agents through semi-synthetic approaches.
Asunto(s)
Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Neoplasias del Colon/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Flavonoides/farmacología , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Puntos de Control de la Fase M del Ciclo Celular/efectos de los fármacos , Propiofenonas/farmacología , Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Células Tumorales Cultivadas , Proteínas ras/metabolismoRESUMEN
BACKGROUND: Zhuyeqing Liquor (ZYQL), a well-known Chinese traditional health liquor, has various biological properties, including anti-oxidant, anti-inflammatory, immunoenhancement and cardiovascular protective effects. METHODS: The protective effects of Zhuyeqing Liquor (ZYQL) on the immune function was investigated in vivo in normal healthy mice and immunosuppressed mice treated with Cyclophosphamide (Cy, 100 mg/kg) by intraperitoneal injection on days 4, 8 and 12. ZYQL (100, 200 and 400 mg/kg) was administered via gavage daily for 14 days. The phagocytotic function of mononuclear phagocytic system was detected with carbon clearance methods, the levels of interleukin-6 (IL-6) and interferon-gamma (IFN-γ) in serum were detected with Enzyme linked immunosorbent assay (ELISA). Immune organs were weighed and organ indexes (organ weight/body weight) of thymus and spleen were calculated. Meanwhile, the activity of lysozyme (LSZ) in serum and the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) in spleen tissue were measured. RESULTS: ZYQL significantly upgrades the K value for clearance of carbon particles in normal mice treated with ZYQL (400 mg/kg) and immunosuppressed mice treated with ZYQL (100, 200 and 400 mg/kg) together with Cy (100 mg/kg) in vivo. The treatment of ZYQL (100, 200 and 400 mg/kg) effectively increased the activity of serum lysozyme as well as promoted the serum levels of IL-6 and IFN-γ in normal mice and immunosuppressed mice. Furthermore, ZYQL (100, 200 and 400 mg/kg) had an antioxidant effects in immune system by enhancing the antioxidant enzyme activity of SOD, CAT and GSH-Px in vivo. In addition, ZYQL (100, 200 and 400 mg/kg) effectively elevated the Cy-induced decreased organ index (thymus and spleen). CONCLUSIONS: The present work shows that the dose-dependent administration of ZYQL is capable of influencing immune responses, which implying that its valuable functional health may be attributed partly to its protective effects for the immune function.