Retinoic acid and arsenic trioxide sensitize acute promyelocytic leukemia cells to ER stress

Silvia Masciarelli, E. Capuano, T. Ottone, M. Divona, S. De Panfilis, C. Banella, N. I. Noguera, A. Picardi, G. Fontemaggi, G. Blandino, F. Lo-Coco, F. Fazi

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Retinoic acid (RA) in association with chemotherapy or with arsenic trioxide (ATO) results in high cure rates of acute promyelocytic leukemia (APL). We show that RA-induced differentiation of human leukemic cell lines and primary blasts dramatically increases their sensitivity to endoplasmic reticulum (ER) stress-inducing drugs at doses that are not toxic in the absence of RA. In addition, we demonstrate that the PERK pathway, triggered in response to ER stress, has a major protective role. Moreover, low amounts of pharmacologically induced ER stress are sufficient to strongly increase ATO toxicity. Indeed, in the presence of ER stress, ATO efficiently induced apoptosis in RA-sensitive and RA-resistant APL cell lines, at doses ineffective in the absence of ER stress. Our findings identify the ER stress-related pathways as potential targets in the search for novel therapeutic strategies in AML.
Original languageEnglish
Pages (from-to)285-294
Number of pages10
JournalLeukemia
Volume32
DOIs
Publication statusPublished - 2018

Keywords

  • Antineoplastic Agents
  • Apoptosis
  • Arsenic Trioxide
  • Cell Differentiation
  • Cell Line
  • Cell Line, Tumor
  • Endoplasmic Reticulum Stress
  • HEK293 Cells
  • Humans
  • Leukemia, Promyelocytic, Acute
  • Tretinoin

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