Protection of acute myeloid leukaemia cells from apoptosis induced by front-line chemotherapeutics is mediated by haem oxygenase-1

Haem oxygenase-1 (HO-1) is increasingly regarded as a pro-tumoral target in the treatment of human cancers. Currently, little is known about HO-1 and its role in human acute myeloid leukaemia (AML) to regulate apoptosis in response to chemotherapy. Recently, we showed that HO-1 protects AML samples from tumour necrosis factor-α (TNF)-induced apoptosis - it being regulated by transcription factors Nrf2, NF-κB and AP-1. This study aims to analyse the role of HO-1 in regulating apoptosis in AML cells in response to two front-line chemotherapeutic agents used for AML, cytarabine and daunorubicin. Here we show that HO-1 expression in AML samples was increased in response to both cytarabine and daunorubicin treatment, and micro RNA (miRNA) silenced HO-1 expression in combination with either daunorubicin or cytarabine induced a greater apoptotic responses in AML cells. Moreover, we showed that both daunorubicin and cytarabine induced reactive oxygen species (ROS) accumulation to induce apoptosis in AML. However, ROS-dependent induction of HO-1 was limiting the apoptotic response that is seen in AML towards cytarabine and daunorubicin treatment. These findings suggest concurrent inhibition of HO-1 expression in conjunction with chemotherapeutic treatment would improve the number of cases who reach complete remission.

• Publication year

  2011

• Venue

  OncoTarget

• Publication date

  2011-09-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.18632/ONCOTARGET.321PMID 21911919PMCID 3248221
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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