Beta-Lapachone Attenuates BMSC-Mediated Neuroblastoma Malignant Transformation by Inhibiting Gal-3/Gal-3BP/IL6 Axis

Abstract

The inflammatory factor IL6 secreted by bone marrow mesenchymal stem cells (BMSCs) in the tumor microenvironment (TME) facilitates the survival and therapeutic resistance of neuroblastoma (NB). Here, we found that IL6 expression in primary tumor tissues or bone marrow (BM) metastases was closely associated with the disease risk and prognosis of NB patients. IL6 secretion from immortalized BMSC (iBMSC) was directly regulated by NB cells and is involved in promoting the proliferation and metastasis of NB cells. Beta-Lapachone (ARQ-501, LPC), an ortho-naphthoquinone natural product, significantly prevented the iBMSC-induced malignant transformation effect on NB cells through suppressing the expression and secretion of IL6 from iBMSC in vitro and in vivo. Mechanistically, LPC disrupted the crosstalk between NB cells and iBMSC in an NQO1-dependent manner through blocking the Gal-3/Gal-3BP/IL6 axis. Our results reveal the effect of iBMSC-derived IL6 on TME-induced malignant transformation of NB cells, and provide theoretical basis for the clinical application of LPC as a potential IL6 inhibitor in high-risk refractory NB patients.

β‐lapachone protects against doxorubicin‐induced hepatotoxicity through modulation of NAD+/SIRT‐1/FXR/p‐AMPK/NF‐kB and Nrf2 signaling axis

“…The administration of β-LAP is logical if it does not interfere with the anticancer effects of DOX. Several studies have shown promising antitumor activity of β-LAP against various tumor types, particularly neuroblastoma, [42] breast cancer, [43] melanoma, [44] oral squamous cell carcinoma, [45] and so forth.…”

“…The administration of β‐LAP is logical if it does not interfere with the anticancer effects of DOX. Several studies have shown promising antitumor activity of β‐LAP against various tumor types, particularly neuroblastoma, [ 42 ] breast cancer, [ 43 ] melanoma, [ 44 ] oral squamous cell carcinoma, [ 45 ] and so forth. Taken together, our results demonstrate that β‐LAP not only suppresses NF‐kB signaling pathway but also activates Nrf2 signaling pathway via modulation of NAD + /SIRT‐1/FXR/AMPK axis.…”

The Antigastric Cancer Effect of Triptolide is Associated With H19/NF-κB/FLIP Axis

“…Cell transfection was carried out according to our published research ( Zhou Y. et al, 2021 ). Briefly, for gene silencing of miR-204-5p or overexpression of human FLIP and H19, miRNA inhibitor or plasmid carrying the corresponding sequence were purchased from Genepharma (Shanghai, China).…”

Nanotechnology-Based Diagnostic and Therapeutic Strategies for Neuroblastoma

“…As an essential component of TME, the ECM is known to be a dense network with structural proteins, bridging proteins, proteoglycans and enzymes that mainly provide biochemical and structural support for tumorigenesis and progression ( Ho et al, 2020 ; Gonzalez-Molina et al, 2022 ; Jiang et al, 2022 ). Various chemokines, inflammatory factors, cytokines and growth factors secreted from TME-associated inflammatory cells or stromal cells collectively constitute a dynamic microhabitat possessing diverse functional states through crosstalk with the ECM ( Wohlrab et al, 2014 ; Zhou et al, 2021 ). The aberrantly overexpressed ECM components in TME appear to be associated with stronger pro-invasive, pro-metastatic and pro-proliferative capacities of NB.…”