Poly ADP-ribose polymerase inhibition suppresses cisplatin toxicity in chronic myeloid leukemia cells

Ling Yi Xiao, Wai Ming Kan

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Cancer cells may acquire drug resistance by activating DNA repair signaling. Poly ADP-ribose polymerase (PARP) plays an important role in DNA repair and it is overexpressed in many cancers including chronic myeloid leukemia (CML). PARP inhibitors have been used either alone or with other drugs to augment cancer cell death. However, whether PARP inhibitors may also augment cell death induced by chemotherapeutic agents in CML cells has not been studied. K562 cells with or without PARP-1 knockdown were treated with cisplatin alone or together with olaparib. The cell death was investigated by propidium iodide staining and apoptosis-related proteins were detected by western blotting. Olaparib suppressed cisplatin-induced cell death in K562 and MEG01 cells. Moreover, PARP-1 knockdown also attenuated cisplatin toxicity in CML cells. Inhibition of PARP decreased cisplatin toxicity by attenuating caspase-3 and caspase-9 activity. These results indicated that the toxicity of cisplatin in CML cells requires PARP activity. Therefore, PARP inhibitors may not be useful with DNA-damaging agents such as cisplatin in CML treatment. Anti-Cancer Drugs 28:316-321.

Original languageEnglish
Pages (from-to)316-321
Number of pages6
JournalAnti-Cancer Drugs
Volume28
Issue number3
DOIs
Publication statusPublished - 2017 Jan 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research

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