RESUMEN
Malachite green (MG) induces DNA damage and malignant transformation of Syrian hamster embryo (SHE) cells in primary culture. In the present study, we have studied the role of all the three isoforms of mitogen activated protein (MAP) kinases i.e. ERK (extracellular regulated kinase), JNK (JUN- N- terminal kinase) and p38 kinase during transformation of SHE cells by MG. The results showed that transformed cells were associated with a decreased expression of phosphoactive ERK and JNK and increased expression of p38 kinase as evident from the Western blot, immunofluorescence and flow cytometry studies. Also, a persistent nuclear localization of p38 kinase was observed in the transformed cells. The present study indicated that p38 kinase was present at higher levels and seemed to be associated with transformation, which suggested that inhibitors of p38 kinase could serve in general as potential agents for selective cancer therapy.
Asunto(s)
Animales , Northern Blotting , Western Blotting , Técnicas de Cultivo de Célula , Ciclo Celular/efectos de los fármacos , Línea Celular Transformada , Núcleo Celular/efectos de los fármacos , Colorantes/toxicidad , Cricetinae , Ciclina D1/genética , Citoplasma/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/biosíntesis , Fibroblastos/citología , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Expresión Génica/efectos de los fármacos , Isoenzimas , Proteínas Quinasas JNK Activadas por Mitógenos/biosíntesis , Mesocricetus , Colorantes de Rosanilina/toxicidad , Proteínas Quinasas p38 Activadas por Mitógenos/biosíntesisRESUMEN
In the present study, anti-proliferative effects of dietary polyphenolic compounds have been observed and demonstrated the strong anticancer efficacy of curcumin (CMN), an active constituent of dietary spice (turmeric) using human leukemia cancer cell line. CMN inhibited the proliferation of K562 leukemic cells by induction of apoptosis. The current study demonstrated synergy with combination of drug therapy, and suggested that combination of ferulic acid and cisplatin synergistically inhibited cellular proliferation. Cytotoxic synergy was observed independent of the sequence of addition of two drugs to cultured cells. The synergized growth inhibitory effect with cisplatin was probably associated with G2-M arrest in cell cycle progression. These findings suggested that among the cinnamoyl compounds, CMN was most potent and FER appeared to be a better modulating agent on human malignant cell line.