Related Experiment Video

Updated: May 4, 2026

Zebrafish Model of Neuroblastoma Metastasis
05:20

Zebrafish Model of Neuroblastoma Metastasis

Published on: March 14, 2021

2.5K

HO-1 up-regulation: a key point in high-risk neuroblastoma resistance to bortezomib

Anna Lisa Furfaro1, Sabrina Piras1, Mario Passalacqua1

  • 1Department of Experimental Medicine, University of Genoa, 2, L.B. Alberti Street, I-16132 Genoa, Italy.

Biochimica Et Biophysica Acta
|January 2, 2014
PubMed

Insights

Inhibition of heme oxygenase-1 (HO-1) enhances bortezomib (BTZ) therapy effectiveness in high-risk neuroblastoma (NB) by overcoming chemoresistance. HO-1 upregulation serves as a marker for chemoresistance in NB.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • High-risk neuroblastoma (NB) exhibits chemoresistance, often linked to the Nrf2/HO-1 pathway.
  • Bortezomib (BTZ), a proteasome inhibitor, is explored to overcome drug resistance in NB.
  • The nuclear factor-erythroid-derived 2-like 2 (Nrf2) and heme oxygenase-1 (HO-1) pathway influences cancer cell antioxidant and detoxification capabilities.

Purpose of the Study:

  • Investigate the role of Nrf2 and HO-1 in NB cell lines with varying aggressiveness when treated with BTZ.
  • Focus on modulating HO-1 to enhance sensitivity to BTZ therapy in high-risk neuroblastoma.
  • Determine if HO-1 inhibition can improve the efficacy of proteasome inhibitor-based therapy.

Main Methods:

  • Treatment of MYCN-amplified (HTLA-230) and MYCN non-amplified (SH-SY5Y) neuroblastoma cell lines with bortezomib (BTZ).
  • Assessment of Nrf2 activation and HO-1 expression levels in response to BTZ.
  • Inhibition of HO-1 activity using Zinc (II) protoporphyrin IX (ZnPPIX) to evaluate its impact on BTZ efficacy.
  • Analysis of p53 and p21 modulation in BTZ-treated cells.

Main Results:

  • MYCN-amplified HTLA-230 cells showed limited sensitivity to BTZ due to Nrf2 activation and subsequent HO-1 upregulation.
  • BTZ treatment in HTLA-230 cells led to p53 downregulation and p21 upregulation, promoting cell survival.
  • Inhibition of HO-1 with ZnPPIX significantly enhanced BTZ's pro-apoptotic effect independently of p53 and p21.
  • MYCN non-amplified SH-SY5Y cells were more sensitive to BTZ, correlating with their inability to upregulate HO-1.

Conclusions:

  • HO-1 inhibition improves the sensitivity of aggressive neuroblastoma to proteasome inhibitor therapy.
  • HO-1 upregulation can serve as a predictive marker for chemoresistance in neuroblastoma.
  • Targeting the HO-1 pathway offers a potential strategy for combined therapy to overcome chemoresistance in high-risk NB.
Keywords:
ChemoresistanceHeme oxygenase-1NeuroblastomaRedox signaling

More Related Videos

Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy09:40

Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy

Published on: October 4, 2019

5.2K
Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions09:17

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions

Published on: August 2, 2018

17.4K

Related Concept Videos

Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.0K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.6K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.9K