Prenylterphenyllin, a regulator of P53, inhibits colorectal cancer progression through oxidative stress and energy metabolism pathway.

Colorectal cancer (CRC) is one of the most prevalent and deadly cancers globally, with poor prognosis primarily due to metastasis and resistance to conventional therapies. This study evaluated the antitumor potential of prenylterphenyllin, a natural product derived from Aspergillus candidus. Prenylterphenyllin significantly reduced CRC cells viability and migration, while promoting apoptosis and cell-cycle arrest. Transcriptomic analysis showed activation of the p53 signaling pathway and inhibition of cell-cycle-related genes. Prenylterphenyllin also disrupted mitochondrial function and oxidative phosphorylation, increasing oxidative stress. In vivo, it suppressed tumor growth and lung metastasis without notable toxicity. These results highlight that prenylterphenyllin is a promising candidate for CRC therapy, capable of inhibiting tumor growth, migration, and metastasis while inducing apoptosis through the modulation of energy metabolism and oxidative stress. As a promising candidate, prenylterphenyllin may offer new therapeutic opportunities for CRC, particularly for metastatic disease. Collectively, this study identifies prenylterphenyllin as a novel therapeutic candidate for CRC and illuminates its promising therapeutic potential.