RESUMEN
High risk human papillomavirus (HPV) is a well recognized causative agent of cervical cancer. Suberoylanilide hydroxamic acid (SAHA) is a potential anti-cervical cancer drug; however, its effect on the expression of HPV E6 and E7 genes remains unclear. Here, we show that, in SAHA treated HeLa cells, HPV18 E6 and E7 mRNA and protein levels were reduced, HPV18 promoter activity was decreased, and the association of RNP II with HPV18 promoter was diminished, suggesting that SAHA inhibited the transcription initiation of HPV18 E6 and E7 genes. In SAHA-treated HeLa, although the level of lysine 9-acetylated histone H3 in the whole cell extracts increased obviously, its enrichment on HPV18 promoter was significantly reduced which is correlated with the down-regulation of HPV E6 and E7.
Asunto(s)
Alphapapillomavirus/genética , Proteínas de Unión al ADN/genética , Genes Virales , Ácidos Hidroxámicos/farmacología , Proteínas Oncogénicas Virales/genética , Transcripción Genética/efectos de los fármacos , Neoplasias del Cuello Uterino/virología , Secuencia de Bases , Cartilla de ADN , Femenino , Células HeLa , Humanos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias del Cuello Uterino/patología , VorinostatRESUMEN
Warburg effect is a dominant phenotype of most cancer cells. Here we show that this phenotype depends on its environment. When cancer cells are under regular culture condition, they show Warburg effect; whereas under lactic acidosis, they show a nonglycolytic phenotype, characterized by a high ratio of oxygen consumption rate over glycolytic rate, negligible lactate production and efficient incorporation of glucose carbon(s) into cellular mass. These two metabolic modes are intimately interrelated, for Warburg effect generates lactic acidosis that promotes a transition to a nonglycolytic mode. This dual metabolic nature confers growth advantage to cancer cells adapting to ever changing microenvironment.