Cell Painting Identifies Flavonoids That Are Toxic to Bladder Cancer Cells

Source: Baylor College of Medicine
URL: https://www.bcm.edu/news/cell-painting-identifies-flavonoids-that-are-toxic-to-bladder-cancer-cells

Researchers used Cell Painting technology to identify six flavonoids that demonstrate toxicity against bladder cancer cell lines, with three compounds showing selective activity against cancer cells while sparing normal bladder tissue. Xanthohumol, found in certain beers, emerged as a particularly promising candidate that disrupts lipid metabolism in cancer cells without affecting DNA.

Notably, we discovered that xanthohumol-induced killing of bladder cancer cells was accompanied by a decrease in lipid metabolism in these cells and a stark reduction in the number of lipid droplets per cell.

– Dr. Michael J. Bolt

Study Design & Population

  • Study Type: Laboratory-based drug screening using Cell Painting microscopy
  • Sample: 244 flavonoid compounds tested across three bladder cancer cell lines
  • Technology: SPACe (Swift Phenotypic Analysis of Cells) computational analysis
  • Models: 2D cell cultures, 3D spheroids, and chorioallantoic membrane systems

Key Findings

  • Six flavonoids demonstrated bladder cancer cell toxicity, including two known compounds (flavopiridol and rotenone)
  • Three compounds selectively killed cancer cells while preserving normal bladder cell growth
  • Multiple mechanisms identified: DNA damage induction and mitochondrial dysfunction
  • Xanthohumol specifically reduced lipid droplets per cell and altered lipid metabolism
  • Four compounds (deguelin, cardamonin, biochannin A, xanthohumol) showed toxicity without DNA damage

Clinical Implications

  • Provides novel screening platform for identifying natural anti-cancer compounds from dietary sources
  • Suggests potential for developing flavonoid-based adjuvant therapies for bladder cancer treatment
  • Opens investigation into protective effects of xanthohumol-rich beer consumption patterns
  • Enables laboratories with standard computing resources to conduct large-scale drug screening

Limitations

  • Pre-clinical stage only: No animal model or human safety data available
  • Laboratory conditions: Cell culture results may not translate to clinical efficacy
  • Mechanism specificity: Limited understanding of why certain flavonoids spare normal cells
  • Future validation required: Animal studies and clinical trials needed before therapeutic application

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