Apoptosis-resistant phenotype in HL-60-derived cells HCW-2 is related to changes in expression of stress-induced proteins that impact on redox status and mitochondrial metabolism

S. Salvioli, G. Storci, M. Pinti, D. Quaglino, L. Moretti, M. Merlo-Pich, G. Lenaz, S. Filosa, A. Fico, M. Bonafè, D. Monti, L. Troiano, M. Nasi, A. Cossarizza, C. Franceschi

Research output: Contribution to journalArticle

Abstract

The onset of resistance to drug-induced apoptosis of tumour cells is a major problem in cancer therapy. We studied a drug-selected clone of promyelocytic HL-60 cells, called HCW-2, which display a complex resistance to a wide variety of apoptosis-inducing agents and we found that these cells show a dramatic increase in the expression of heat shock proteins (Hsps) 70 and 27, while the parental cell line does not. It is known that stress proteins such as Hsps can confer resistance to a variety of damaging agents other than heat shock, such as TNF-α, monocyte-induced cytoxicity, and also play a role in resistance to chemotherapy. This elevated expression of Hsps is paralleled by an increased activity of mitochondrial metabolism and pentose phosphate pathway, this latter leading to high levels of glucose-6-phosphate dehydrogenase and, consequently, of glutathione. Thus, the apoptotic-deficient phenotype is likely because of the presence of high levels of stress response proteins and GSH, which may confer resistance to apoptotic agents, including chemotherapic drugs. Moreover, the fact that in HCW-2 cells Hsp70 are mainly localised in mitochondria may account for the increased performances of mitochondrial metabolism. These observations could have some implications for the therapy of cancer, and for the design of combined strategies that act on antioxidant defences of the neoplastic cell.

Original languageEnglish
Pages (from-to)163-174
Number of pages12
JournalCell Death and Differentiation
Volume10
Issue number2
DOIs
Publication statusPublished - Feb 1 2003

    Fingerprint

Keywords

  • Apoptosis
  • Cancer
  • Mitochondrial metabolism
  • Multidrug resistance
  • Stress proteins

ASJC Scopus subject areas

  • Cell Biology

Cite this

Salvioli, S., Storci, G., Pinti, M., Quaglino, D., Moretti, L., Merlo-Pich, M., Lenaz, G., Filosa, S., Fico, A., Bonafè, M., Monti, D., Troiano, L., Nasi, M., Cossarizza, A., & Franceschi, C. (2003). Apoptosis-resistant phenotype in HL-60-derived cells HCW-2 is related to changes in expression of stress-induced proteins that impact on redox status and mitochondrial metabolism. Cell Death and Differentiation, 10(2), 163-174. https://doi.org/10.1038/sj.cdd.4401124