Differential Suppression of Human Cervical Cancer Cell Growth by Adenovirus Delivery of p53 in vitro: Arrest Phase of Cell Cycle Is Dependent on Cell Line

Abstract

It has been reported that overexpression of wild-type p53 protein induces suppression of tumor cell growth in vivo and in vitro. In this study, we further evaluated the differential effects of p53 delivered in an adenovirus vector on the cell growth, apoptosis and cell cycle progression in cervical cancer cell lines. We constructed a recombinant adenovirus expressing p53 and then delivered this into cervical carcinoma cell lines (CaSki, SiHa, and HeLa, HeLaS3) along with adenovirus expressing β β β β-galactosidase as a negative control. Adenovirus-delivered p53 overexpression resulted in a more significant suppression of cell growth in HPV 18-infected cells (HeLa and HeLaS3) and a lesser suppression in HPV 16-infected cells (CaSki and SiHa). However, no suppression was observed in cells infected with a negative control virus. p53 overexpression also induced apoptosis and cell cycle arrest, as determined by annexin V and propidium iodide staining. In particular, the cell cycle was arrested in the G 2 /M phase in CaSki cells. In contrast, cell cycles were arrested in the G 1 phase in HeLa cells, suggesting that the arrest phase is dependent upon the cervical cancer cell line. Taken together, these data support the idea that overexpressed p53 protein plays a differential role in suppressing cervical cancer cell growth through apoptosis and cell cycle arrest in either G 1 or G 2 /M phase, depending on the cancer cell line.

Honeybee venom possesses anticancer and antiviral effects by differential inhibition of HPV E6 and E7 expression on cervical cancer cell line

“…Treatment of melittin also potently induced pro-apoptotic protein p53, Bax and caspase-3 expression but decreased anti-apoptotic protein Bcl-2 expression (27). We also observed that p53 overexpression induced apoptosis in CaSki and HeLa cells, as determined by Annexin V staining (28). This is consistent with our observation that both CaSki and HeLa cells displayed cell death upon BV treatment with the downregulation of E6/E7 protein of HPV16/18, and BV treatment behaves differently in HeLa and CaSki cells.…”

Treatment of hepatocellular carcinoma by AdAFPep/rep, AdAFPep/p53, and 5-fluorouracil in mice

“…1C). 30 to 50 MOI were used for nlacZ transfection 40,41 and expression experiments and second on the fact that evidence in the present study indicated that a 10:1 ratio of AdAFPep/nlacZ to AdAFPep/Rep was most appropriate for increasing transgene expression (shown later in Fig. 6).…”

Cytotoxicity of Docetaxel (Taxotere^®) Used as a Single Agent and in Combination with Radiation in Human Gastric, Cervical and Pancreatic Cancer Cells

“…Differential sensitivity of BRCA-2-defective Capan-1 vs. BRCA-2 normal BxPC-3 cells to ionizing radiation was attributed to the effect of BRCA-2 on DNA double-strand break repair [45,46] . Although a signifi cant difference in sensitivity between CaSki and HeLa cells has been noted previously, the underlying mechanisms remain unclear [56] . The CaSki or HeLa cell lines are both human papillomavirus (HPV)-positive, but differ in the number of HPV copies per cell (CaSki: 600 HPV copies per cell, HeLa: 50 HPV copies per cell), and consequently differ in the number of viral E6 and E7 oncoproteins; these proteins may interfere by binding with normal functions of p53 or pRb [40,56] .…”