Biochem Biophys Res Commun 2001 (Mar 30); 282 (2): 409–15
Reddy VG, Khanna N, Singh N
Department of Biochemistry,
All India Institute of Medical Sciences,
New Delhi, India
Human Papilloma Virus (HPV) is associated in most instances with cervical cancer. The HPV oncoproteins target P53 protein for degradation, leading to deregulation of cell cycle. We investigated whether stabilization of P53 in cervical cancer cells, by downregulating HPV transcription would restore the apoptotic ability of these cells. Our findings show that vitamin C downregulates the redox sensitive transcription factor AP-1 and decreases one of its transcription targets HPV E6, and stabilizes P53. This was associated with an increase in Bax and decrease in Bcl-2 and telomerase activity. Accumulation of P53 and its target gene bax then sensitized HeLa cells to cell-cycle arrest, cell death/apoptosis induced by cisplatin, and etoposide. Increasing drug sensitivity of cervical carcinoma cells by stabilizing P53 using vitamin C is a novel approach and has potential clinical relevance.