Cisplatin-resistant HeLa cells are resistant to apoptosis via p53-dependent and -independent pathways

Yukihisa Minagawa, Junzo Kigawa, Hiroaki Itamochi, Yasunohu Kanamori, Muneaki Shimada, Masakuni Takahashi, Naoki Terakawa

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Since HeLa cells possess very little functional p53 activity, they could be originally resistant to genotoxic stress-induced apoptosis. Therefore, it is likely that the drug-resistant cells derived from HeLa cells are more resistant to apoptosis. The aim of this study was to determine whether cisplatin-resistant cells derived from HeLa cells have an apoptosis-resistant phenotype. A cisplatin-resistant cell subline, HeLa/CDDP cells, showed a 19-fold resistance to cisplatin compared with the parent cells. The subline showed a collateral sensitivity to paclitaxel. An equitoxic dose (IC50) of cisplatin produced DNA fragmentation in HeLa cells but not in HeLa/CDDP cells. Transfection of wild-type p53 gene enhanced the cytotoxicity of cisplatin and cisplatin-induced apoptosis in HeLa cells but not in HeLa/CDDP cells, although it caused p53 overexpression in both cell lines. The expression of caspase 1 (interleukin-1β-converting enzyme, ICE) mRNA and the overexpression of bax protein were observed only in HeLa cells. Paclitaxel-induced DNA fragmentation appeared less in HeLa/CDDP cells than in HeLa cells. p53 gene transfection did not affect the extent of DNA fragmentation in either cell line, suggesting that paclitaxel may induce p53-independent apoptosis. These findings suggest that HeLa/CDDP cells may have an acquired phenotype that is resistant to p53-dependent and -independent apoptosis.

Original languageEnglish
Pages (from-to)1373-1379
Number of pages7
JournalJapanese Journal of Cancer Research
Volume90
Issue number12
DOIs
Publication statusPublished - 1999 Dec

Keywords

  • Apoptosis
  • Cisplatin
  • Drug-resistance
  • HeLa cells
  • p53

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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