Curcumin, berberine, and other plant-based compounds have long been of scientific interest due to their anti-inflammatory and anticancer properties. However, a new study by researchers from the Wrocław University of Medicine and the University of Wrocław has shown that not all natural compounds work the same, and that strong anticancer activity does not necessarily go hand in hand with a good safety profile.
The researchers compared five compounds: curcumin, berberine, biochanin A, cucurbitacin E, and CAPE (caffeic acid phenethyl ester), a component of propolis. They investigated how these substances affected fibrosarcoma cells and healthy muscle cells.
cellular control switch
This study focused on the NF-κB signaling pathway, which regulates inflammation, metabolism, cell survival, and cellular senescence.
NF-κB acts like a central control switch that integrates cellular stress signals, determining whether cells activate inflammatory pathways, fight for survival, or alter their metabolism. ”
Professor Julita Kulbacka, Department of Molecular and Cell Biology, Wrocław Medical University
In cancer cells, overactivation of this pathway may promote survival and adaptation to adverse conditions. At the same time, since NF-κB is essential for normal cellular function, the goal is not to switch it off completely, but to modulate its activity as precisely as possible.
Cancer cells struggled even more with energy depletion
The compounds tested disrupted mitochondrial function and reduced the cells’ ability to produce energy.
In fibrosarcoma cells, ATP levels were reduced by about 83 to 92%, while in healthy muscle cells they were reduced by about 23 to 73%. This suggests that cancer cells are more vulnerable to disturbances in energy metabolism.
These compounds also affected mitophagy, the process that removes damaged mitochondria.
Berberine, cucurbitacin E, and CAPE enhanced PINK1/PARKIN-dependent mitophagy in fibrosarcoma cells. Combined with a marked drop in ATP levels, this indicates an overactive adaptive mechanism that leads to cell aging and death, rather than a defensive response, says Professor Julita Kulbacka.
cancer cells have stopped dividing
All five compounds induced cellular senescence features in fibrosarcoma cells. In this condition, the cells remain alive but permanently lose their ability to divide.
The strongest effect was observed with curcumin. The proportion of senescent cancer cells increased from approximately 16.5% to more than 75%. For other compounds, the percentage was also higher than 66%.
Healthy muscle cells generally showed a weak response, suggesting some degree of selectivity towards cancer cells.
Curcumin showed the best overall balance
Cell viability experiments demonstrated that curcumin and CAPE exhibited the highest selectivity for fibrosarcoma cells. Curcumin combined potent anticancer activity and induction of cellular senescence while maintaining a relatively good safety profile.
Our findings indicate that these natural compounds can selectively place a greater metabolic burden on cancer cells than on healthy cells by interfering with mitochondrial function and energy metabolism. Among the compounds tested, curcumin showed the most balanced profile, emphasizes Professor Julita Kulbacka.
Berberine was also well tolerated, but its effects on mitochondria in healthy muscle cells require further investigation.
Effect alone is not enough
To assess safety, the researchers also used larvae of the cane moth (Galleria mellonella) as an early toxicity model.
Berberine and curcumin were the most well-tolerated compounds. CAPE and cucurbitacin E increased mortality, but biochanin A was found to be the most toxic.
These findings demonstrate that potent anticancer activity alone is not sufficient for a compound to be a promising drug candidate. Safety for the whole organism is equally important.
this is not a cure yet
This result does not mean that curcumin, berberine, or other tested compounds can already be used to treat sarcoma. This study was conducted using animal cell lines and simple invertebrate models.
Our findings come from laboratory experiments and preliminary tests on wax moth larvae. The next step is to evaluate these compounds in more advanced in vivo models to better understand their mechanisms of action and optimal methods of administration and delivery, Klubacka points out.
Nevertheless, this study identifies compounds worthy of further investigation and highlights why the evaluation of natural anticancer drugs should consider not only their efficacy against cancer cells, but also their effects on healthy tissues and the whole organism.
sauce:
Wroclaw Medical University
Reference magazines:
Lazka, J. others. (2026). Modulation of NFκB signaling by natural compounds in sarcoma and normal muscle models. International Journal of Molecular Sciences. DOI: 10.3390/ijms27115025. https://www.mdpi.com/1422-0067/27/11/5025
