Mumio Potentiates Temozolomide by Inducing Apoptosis and Ferroptosis in Glioblastoma Cells.
TL;DR
Findings suggest that Mumio exerts anticancer effects through oxidative stress-mediated apoptosis and modulation of ferroptosis pathways, suggesting its potential use alongside standard therapy.
Abstract
INTRODUCTION Glioblastoma multiforme is an extremely deadly, aggressive primary brain tumor, distinguished by poor prognosis, and the rapid development of resistance to temozolomide might be the cause of low survival. Novel adjunctive strategies are needed to enhance therapeutic efficacy. Mumio (Shilajit), rich in fulvic acid and bioactive compounds, has shown antioxidant and anticancer effects, but its role in glioblastoma remains unclear. This study evaluated its anticancer potential and its ability to enhance temozolomide efficacy.
Methods
Mumio extract was tested in U87 (sensitive) and LN-18 (resistant) glioblastoma cell lines. Cell viability and clonogenicity were assessed by MTT and colony formation assays. Fluorescent staining evaluated mitochondrial function, reactive oxygen species, and lipid accumulation. Western blotting analyzed apoptotic (PARP, Caspase-3, PTEN), ferroptosis-related (NRF2, FTH1), and Akt signaling proteins. Combination treatments were also examined.
Results
Mumio reduced cell viability in a dose- and time-dependent manner, with stronger effects in U87 cells. It increased reactive oxygen species, disrupted mitochondrial function, and induced apoptosis, as shown by increased cleaved PARP and Caspase-3. Ferroptosis-related changes, including reduced FTH1 in LN-18 cells, were observed. Mumio also enhanced temozolomide-induced cytotoxicity and reduced clonogenic survival.
Discussion
These findings suggest that Mumio exerts anticancer effects through oxidative stress-mediated apoptosis and modulation of ferroptosis pathways. Its ability to enhance temozolomide efficacy, particularly in resistant cells, indicates a potential role in overcoming chemoresistance.
Conclusion
Mumio triggers apoptosis in glioblastoma cells and induces changes consistent with ferroptosis, while also chemosensitizing cells to temozolomide, suggesting its potential use alongside standard therapy.