A phenotypic screen identifies xanthohumol and other flavonoids as killers of bladder cancer

Area of Science:

• Oncology
• Pharmacology
• Biotechnology

Background:

• Bladder cancer is a common diagnosis in the US, with current treatments including trans-urethral resection of bladder tumors (TURBT) and immunotherapy with Bacille Calmette-Guerin (BCG).
• Residual tumors after TURBT and limitations of current therapies necessitate novel treatment strategies.

Purpose of the Study:

• To screen a library of 244 flavonoid compounds for their efficacy in targeting bladder cancer cells.
• To identify novel therapeutic candidates and elucidate their mechanisms of action in bladder cancer.

Main Methods:

• Utilized Cell Painting, a high-content imaging technique, to screen flavonoid compounds for cytotoxicity against bladder cancer cells.
• Employed multiparametric analysis (SPACe) to assess compound effects and identify promising candidates.
• Validated hit compounds in spheroid and chorioallantoic membrane models.

Main Results:

• Identified several flavonoid compounds with significant bladder cancer cell toxicity.
• Xanthohumol demonstrated efficacy by reducing cancer cell viability, potentially through altering lipid metabolism.
• Hit compounds showed effectiveness in more complex biological models, including spheroids and chorioallantoic membranes.

Conclusions:

• Flavonoids represent a promising class of compounds for bladder cancer drug discovery.
• Innovative screening methods like Cell Painting are crucial for identifying novel therapeutic agents.
• Potential synergistic effects exist between flavonoids and existing therapies like BCG, suggesting combination strategies for improved bladder cancer treatment.