Molecules Derived From Sea Sponge Show Promising Effects In Cancer, Mitochondrial Function
Arthur T Knackerbracket has processed the following story:
A groundbreaking study led by the USC Leonard Davis School of Gerontology in collaboration with Dominican University of California explores how small molecules derived from sea sponges affect energy production in mitochondria and details their remarkably targeted effects on various types of cancers.
[...] The research focused on mycothiazole (MTZ), a molecule found in the marine sponge C. mycofijiensis, and its synthetic analog 8-O-acetylmycothiazole (8-OAc). These molecules demonstrated significant efficiency in inhibiting the function of electron transport chain (ETC) complex I, a key component of mitochondrial energy production.
The study compared both molecules to the more extensively studied ETC inhibitor rotenone. Mainly used as an agricultural pesticide, rotenone has exhibited anti-cancer properties in human cells in previous studies. However, in this study, rotenone also displayed significant toxicity to non-cancer cells in addition to its effect on cancerous cells.
Both MTZ and 8-OAc exhibited higher toxicity against liver carcinoma, breast cancer, and glioblastoma cells compared to non-cancerous cells in vitro, demonstrating markedly better selectivity than rotenone. Notably, 8-OAc, which is more shelf-stable than MTZ, showed the best selectivity for cancer cells versus healthy cells, highlighting its potential in future therapeutic development, Sanabria said.
"When we test the drugs in human cells, they preferentially target cancer cells for cell death pathways. It does so very robustly; we're getting anywhere from 60% to 80% cell death in cancer cells," they said.
"But when we treat non-cancer cells with the exact same concentrations, we're getting very little effect. Not only are we not seeing any cell death, these drugs basically have no change to the transcriptome of non-cancer cells, which suggests that it's really doing nothing to the non-cancerous cells at the same concentrations that it's able to kill cancer cells."
More information: Naibedya Dutta et al, Investigating impacts of the mycothiazole chemotype as a chemical probe for the study of mitochondrial function and aging, GeroScience (2024). DOI: 10.1007/s11357-024-01144-w
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