Document Type

Article

Publication Date

3-9-2025

Publication Title

Bioengineering (Basel)

Keywords

JGM

JAX Source

Bioengineering (Basel). 2025;12(3):268.

Volume

12

Issue

3

ISSN

2306-5354

PMID

40150732

DOI

https://doi.org/10.3390/bioengineering12030268

Grant

The study was funded by the American Brain Tumor Association Discovery Grant (DG1900023) supported by an Anonymous Family Foundation to M.D.T-S.

Abstract

Medulloblastoma (MB) groups 3 and 4 lack targeted therapies despite their dismal prognoses. Ion channels and pumps have been implicated in promoting MB metastasis and growth; however, their roles remain poorly understood. In this study, we repurposed FDA-approved channel blockers and modulators to investigate their potential anti-tumor effects in MB cell lines (DAOY and D283) and primary cell cultures derived from a patient with MB. For the first time, we report spontaneous calcium signaling in MB cells. Spontaneous calcium signals were significantly reduced by mibefradil (calcium channel blocker), paxilline (calcium-activated potassium channel blocker), and thioridazine (potassium channel blocker). These drugs induced dose-dependent cytotoxicity in both the DAOY and D283 cell lines, as well as in primary cell cultures of a patient with group 3 or 4 MB. In contrast, digoxin and ouabain, inhibitors of the Na/K pump, reduced the calcium signaling by over 90% in DAOY cells and induced approximately 90% cell death in DAOY cells and 80% cell death in D283 cells. However, these effects were significantly diminished in the cells derived from a patient with MB, highlighting the variability in drug sensitivity among MB models. These findings demonstrate that calcium signaling is critical for MB cell survival and that the targeted inhibition of calcium pathways suppresses tumor cell growth across multiple MB models.

Comments

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/ licenses/by/4.0/).

Download

Share

COinS