Researchers at Baylor College of Medicine have identified flavonoids, natural compounds found in plants, that exhibit toxicity to bladder cancer cells cultured in the laboratory. The findings are published in the journal Pharmacological Research - Natural Products. The study utilized Cell Painting technology to identify these compounds and gain insights into their mechanisms of action.
Dr. Michael Mancini, a professor of molecular and cellular biology and director of Baylor’s Integrated Microscopy Core, explained that "Cell Painting uses high-throughput microscopy to highlight cellular structures and, via custom image analysis pipelines, quantify changes in cultured cell populations." This method allows for a detailed understanding of drug interactions with cells by revealing changes within individual internal structures.
The research involved analyzing large datasets generated by Cell Painting analysis, which produces over 57,000 high-throughput confocal images per plate scanned. These datasets are challenging to analyze manually without significant computing resources.
In 2024, Mancini's team developed SPACe (Swift Phenotypic Analysis of Cells), a computational tool designed to analyze thousands of cells across numerous plates and report on subpopulation heterogeneity. Dr. Michael J. Bolt noted that this tool enables large-scale drug screening data sets to be analyzed on standard desktop computers.
The researchers tested 244 flavonoid compounds for their toxicity against bladder cancer cells. They discovered six flavonoids capable of killing the cancer cells; two were already known toxic flavonoids—flavopiridol and rotenone. The SPACe analysis showed that some compounds induced DNA damage while others disrupted mitochondrial functions.
Mancini stated, “Importantly, we also identified three flavonoids that reduced the growth of 3D bladder cancer cultures called spheroid and chorioallantoic membrane systems.” These did not affect normal bladder cell growth but included toxic compounds like deguelin, cardamonin, biochannin A, and xanthohumol.
Bolt highlighted that "xanthohumol-induced killing of bladder cancer cells was accompanied by a decrease in lipid metabolism" with fewer lipid droplets per cell observed.
Xanthohumol is present in certain beers at similar levels used in experiments. Bolt suggested it would be interesting to investigate the incidence of bladder cancer among those who frequently consume xanthohumol-rich beers.
Mancini added that "Flavonoids are found in plants we consume for food and drink," suggesting they may offer natural protection against diseases. Future studies will assess the safety and efficacy of these flavonoids in animal models carrying human tumors before moving on to human clinical trials with an aim toward developing new therapeutic options for improving clinical outcomes.
Jessica Oceguera, Alejandra Rivera Tostado, Christopher D. Candler, Elina Mosa, Kazem Safari, and Maureen G. Mancini also contributed to this work from institutions including Baylor College of Medicine and Texas A&M University.
This research received support from CPRIT-funded GCC Center for Advanced Microscopy and Image Informatics (RP170719) as well as partial funding from the GCC Center for Precision Environmental Health (P30ES030285a) along with additional support from the Dan L Duncan Comprehensive Cancer Center (P30 CA125123).
