3-Hydroxyanthranilic acid suppresses colorectal cancer growth and enhances 5-fluorouracil sensitivity via the YY1–p53 and YY1–DKK4 axes [RNA-Seq 3HAA_5FU_HCT116]

Here, 3-HAA exhibited depleted levels in CRC tissues, and its exogenous administration effectively suppressed the proliferation of multiple CRC cell lines. Through its binding to the Yin Yang 1 (YY1) transcription factor, it disrupted the YY1–p53 interaction, preserved p53 stability, and induced cell cycle arrest.

Notably, in vitro, 3-HAA reduced chemoresistance to the common CRC-chemotherapy drug 5-fluorouracil (5-FU) via the YY1–DKK4 axis. Consistently, in vivo, combined 3-HAA–5-FU treatment effectively inhibited CRC progression, highlighting the potential of 3-HAA for CRC therapy.