Thus, CDV was able to restore the function of p53 and pRb, which are neutralized by the oncoproteins E6 and E7, respectively, in HPV-transformed cells (Andrei et al., 2000). Induction of apoptosis by CDV was confirmed later in several tumor models, including human cancer xenografts in athymic nude mice (Yang et al., 2010 and Abdulkarim et al., 2002). CDV proved to reduce E6

and E7 expression RO4929097 concentration in the HPV-18 positive cervical carcinoma ME-180 cells and in the HEP-2 cells (originally believed to be derived from a head and neck squamous cell carcinoma but later turned out to be HeLa cells) at the transcriptional level with subsequent reactivation of p53 and pRb (Abdulkarim et al., 2002). In a model of stromal-derived factor 1 (SDF-1α)-stimulated invasiveness of HPV-positive cells, CDV had anti-metastatic action which was mediated by inhibition of E6/E7, CXCR4 and Rho/ROCK signalling (Amine et al., 2009). Donne and co-workers tested the effects of CDV on the non-HPV cervical carcinoma cell line C33A compared Selleckchem Ipatasertib to two derived cell

lines, i.e. the C33AT6E6 cells (stable transfected with the low risk HPV6 E6) and the C33AT16E6 cells (stable transfected with the high-risk HPV16 E6). The authors found that CDV treatment had a marked growth-inhibitory effect on high-risk E6 expressing C33AT16E6 cells, supporting the use of CDV for treatment of high-risk HPV-associated diseases. However, unlike high-risk E6, expression of low-risk HPV E6 in C33A cells did not augment the Cell press sensitivity of these cells to CDV. The authors conclude from their studies that CDV may have little

selectivity for low-risk HPV related diseases. However, they based their conclusion only on the expression of one of the viral oncoproteins neglecting the fact that low-risk HPV lesions are due to HPV-induced hyperproliferation resulting from productive HPV infection. On the other hand, Donne’s experiments presumably used newly transfected E6 and E7 expression vectors that had not replicated in the presence of CDV and therefore would not have incorporated CDV to block transcription. On the other hand, they tested the effects of CDV on expression of HPV6b and HPV16 E6 mRNA levels in a system that over-expresses these viral proteins. Also, they used the cervical carcinoma HPV-negative cell line C33A which is also sensitive to the antiproliferative effects of CDV. In contrast to previous results, they found increased HPV E6 RNA levels in C33A cells that over-expressed HPV6b or HPV16 E6 and no selectivity of CDV for HPV-positive cells (Donne et al., 2009 and Donne et al., 2007).