Defining targets of modulation of human tumor cell response to cisplatin

Giovanni Luca Beretta, Laura Gatti, Elisabetta Corna, Nives Carenini, Franco Zunino, Paola Perego

Research output: Contribution to journalArticlepeer-review

Abstract

We previously observed that in yeast cisplatin activates different pathways accounting for stress response. Here, we investigated whether genes involved in yeast drug response were modulated by cisplatin in human tumor cell lines (A2780, IGROV-1, A431, U2-OS) including cisplatin-resistant sublines (A2780/BBR, IGROV-1/Pt1, A431/Pt and U2-OS/Pt). Factors and pathways involved in stress response (glutathione-S-transferase, proteasome, checkpoint control and recombinational repair) were increased by cisplatin in human tumor sensitive and resistant cells. Moreover, sensitization to cisplatin by pharmacologically targeting glutathione or proteasome was observed in sensitive and resistant cells. Interestingly, only in IGROV-1/Pt1 cells, in which cisplatin up-regulated HSP70 and HSP90, targeting of HSP90 resulted in sensitization of resistant cells, suggesting a protective role of stress response. In conclusion, the present findings support the potential relevance of interfering with heat shock protein response to increase cisplatin cytotoxicity in resistant cells. Overall, pathways activated by cisplatin in human tumor cells appear cell-type specific, at least in part reflecting the stress response observed in yeast.

Original languageEnglish
Pages (from-to)1406-1415
Number of pages10
JournalJournal of Inorganic Biochemistry
Volume102
Issue number7
DOIs
Publication statusPublished - Jul 2008

Keywords

  • Cisplatin
  • Human tumor cells
  • Modulation
  • Resistance
  • Stress response

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

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