Down-regulation of p21Waf-1 protein facilitates IR- and UV-induced apoptosis in human squamous carcinoma cells

  • Authors:
    • Shinsuke Izumaru
    • Nobuyuki Arima
    • Yasuo Toyozumi
    • Seiya Kato
    • Minoru Morimatsu
    • Tadashi Nakashima
  • View Affiliations

  • Published online on: May 1, 2004     https://doi.org/10.3892/ijo.24.5.1245
  • Pages: 1245-1255
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

DNA damage via radiation exposure and administration of chemotherapeutic agents induce apoptosis, which is a basic mechanism for non-surgical anti-cancer treatment. We analyzed ionizing radiation (IR)- or ultraviolet (UV)-induced apoptosis in human laryngeal carcinoma (HEp-2) and uterine cervical carcinoma (HeLa) cells, and found that HeLa cells were significantly more sensitive to both IR- and UV-induced apoptosis compared to HEp-2 cells, in spite of the same histological type and p53 status. The cyclin-dependent kinase (Cdk) inhibitor, p21Waf-1 was modified differently between the two cancer cell types, whereas p53 protein was induced in a similar manner after IR or UV treatment. IR steadily induced p21Waf-1 protein in HEp-2 cells, but not in HeLa cells. Additionally, p21Waf-1 protein recovered close to the basal level only in HEp-2 cells, although UV caused rapid, dramatic and caspase-independent reduction of p21Waf-1 protein in both cancer cells. Furthermore, overexpression of p21Waf-1 protein in these cells by transient transfection and in stable cell lines in a tetracycline-regulated system, rescued IR- and UV-induced apoptosis. Finally, suppression of p21Waf-1 protein using antisense oligodeoxynucleotide transfection facilitated UV-induced apoptosis in both HEp-2 and HeLa cells. We concluded that p21Waf-1 protein is modified independently of p53 and functions as an inhibitor of IR- as well as UV-induced apoptosis in squamous carcinoma cells.

Related Articles

Journal Cover

May 2004
Volume 24 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Izumaru, S., Arima, N., Toyozumi, Y., Kato, S., Morimatsu, M., & Nakashima, T. (2004). Down-regulation of p21Waf-1 protein facilitates IR- and UV-induced apoptosis in human squamous carcinoma cells. International Journal of Oncology, 24, 1245-1255. https://doi.org/10.3892/ijo.24.5.1245
MLA
Izumaru, S., Arima, N., Toyozumi, Y., Kato, S., Morimatsu, M., Nakashima, T."Down-regulation of p21Waf-1 protein facilitates IR- and UV-induced apoptosis in human squamous carcinoma cells". International Journal of Oncology 24.5 (2004): 1245-1255.
Chicago
Izumaru, S., Arima, N., Toyozumi, Y., Kato, S., Morimatsu, M., Nakashima, T."Down-regulation of p21Waf-1 protein facilitates IR- and UV-induced apoptosis in human squamous carcinoma cells". International Journal of Oncology 24, no. 5 (2004): 1245-1255. https://doi.org/10.3892/ijo.24.5.1245