Antitumor effect of polyphyllin I (PPI) on colorectal cancer: Evidence from patient-derived organoids and Notch signaling suppression.

ABSTRACT

Colorectal cancer (CRC) is a malignant tumor with a high incidence, ranking first among gastrointestinal malignancies. We investigated the impact of polyphyllin I (PPI), a natural compound found in Paris polyphylla, on CRC. PPI has been documented to exhibit anticancer activity against various tumors. This study aimed to assess the effects of PPI on colorectal cancer and explore its potential mechanisms. Our research demonstrated that PPI inhibited proliferation, promoted apoptosis, and induced G2 cell-cycle arrest in a dose-dependent manner. Additionally, our results indicated that PPI suppressed Notch signaling by downregulating the Notch1 receptor, its ligand Jagged1, and the downstream target Hes1 expression. Furthermore, we confirmed the antitumor effect of PPI on patient-derived organoids. In conclusion, our study indicates that PPI impedes the growth of colon cancer by suppressing the Notch signaling pathway.