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

Risultato della ricerca: Contributo in rivistaArticolo in rivista

20 Citazioni (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.
Lingua originaleEnglish
pagine (da-a)285-294
Numero di pagine10
RivistaLeukemia
Volume32
DOI
Stato di pubblicazionePubblicato - 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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