Regulation of apoptosis reduction in the cisplatin-resistant A431 cell line by Bcl-2 and CPP32

Hiroshi Mese, Akira Sasaki, Rafael E. Alcalde, Shuko Nakayama, Tomohiro Matsumura

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Cisplatin (cis-diamminedichloroplatinum(II), CDDP) is one of the most important chemotherapeutic agents; however, the mechanisms of resistance to this drug are still unknown. Recent reports have demonstrated that chemotherapy can induce apoptosis in some cancer cells, indicating that apoptosis may play a very important role in cancer therapy. Therefore, we used a CDDP-resistant cell line from the human epidermoid carcinoma cell line A431 to investigate whether the modulation of apoptosis influences CDDP resistance. In the CDDP-resistant cell, the cell cycle was not perturbed after CDDP treatment. DNA gel electrophoresis and ELISA of the CDDP-resistant cell showed reduced apoptosis when compared with A431 cells treated with CDDP. We determined the p53, Bcl-2, Bax and CPP32 protein levels by Western blotting. This analysis demonstrated a marked increase in Bcl-2 protein levels and a reduction in CPP32 protein levels in CDDP-resistant cells. Our results indicate that the reduction of apoptosis was one of the CDDP-resistant mechanisms, and that reduced apoptosis in CDDP-resistant cells was influenced by Bcl-2 and CPP32 proteins.

Original languageEnglish
Pages (from-to)69-76
Number of pages8
JournalCHEMOTHERAPY
Volume46
Issue number1
DOIs
Publication statusPublished - 2000

Keywords

  • Apoptosis
  • Bax
  • Bcl-2
  • CPP32
  • Cisplatin resistance
  • p53

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Drug Discovery
  • Pharmacology (medical)
  • Infectious Diseases

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