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.