RESUMO
(-)-Menthol ([1-alpha]-5-methyl-2-[1-methylethyl]-cyclohexanol), is a widely used flavoring ingredient in mouthwash, foods, toothpaste and cigarettes. The studies reported here revealed that (-)-menthol induced cytotoxicity against murine leukemia WEHI-3 cells in vitro in a dose-dependent manner. The effects of (-)-menthol on WEHI-3 cells in vivo (BALBIc mice) were also examined, and it was observed that the Mac-3 and CD11b markers were decreased, indicating inhibition of differentiation of the precursor of macrophage and granulocyte. The weights of liver and spleen samples from mice treated with (-)-menthol were found to be decreased compared to untreated animals.
Assuntos
Leucemia Experimental/tratamento farmacológico , Leucemia Experimental/patologia , Mentol/uso terapêutico , Animais , Peso Corporal/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Leucemia Mielomonocítica Aguda/sangue , Leucemia Mielomonocítica Aguda/tratamento farmacológico , Leucemia Mielomonocítica Aguda/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Mentol/sangue , Mentol/farmacocinética , Mentol/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Baço/efeitos dos fármacos , Baço/patologiaRESUMO
Overexpression of the Ha-ras(val12) oncogene has frequently been detected in primary and metastatic carcinomas. NM23 is a metastasis inhibition factor and plays a suppressive role in metastasis in many types of cancer. In this study, a stable NIH/3T3 cell line harboring an inducible Ha-ras(val12) oncogene (designated as 7-4) and small interfering RNAs (siRNAs) were used to clarify the inverse correlation between nm23 and Ha-ras expression both in vitro and in vivo. A derivative 7-4/Z-3 cell line harboring a ß-galactosidase reporter gene was used to trace cell metastasis in a murine tumor model. The data presented here reveal that Ha-ras(val12) is able to cause cell morphological changes, induce tumor formation, and promote metastasis of tumor cells to the lungs. In mice with metastases, the immune surveillance against tumor formation was suppressed by Ha-ras(val12) overexpression through an increase in T-reg cells and a decrease of cytotoxic T lymphocytes and natural killer cell populations. Our results suggest that the Ha-ras oncogene regulates morphogenesis, tumorigenesis, and metastasis through suppressing nm23 expression and modulation of immune cell function.