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Polyphyllin VII is a steroidal saponin and small molecule natural product extracted from the traditional Chinese medicinal herb Paris polyphylla. It exhibits strong anticancer activity against various carcinomas including lung cancer, breast cancer, prostate cancer, endometrial carcinoma, colon cancer (especially CD44-positive cells), and multiple myeloma. Mechanistically, polyphyllin VII induces autophagic cell death by activating the JNK pathway and inhibiting the PI3K/AKT/mTOR pathway. It also acts as an inhibitor of moesin—a regulator of the Wnt/β-catenin pathway—leading to its degradation via the ubiquitin-proteasome system and suppression of Wnt signaling. Additionally, it can upregulate miR‑33a‑5p to enhance sensitivity to hormone therapies in resistant endometrial carcinoma cells. These actions result in reduced cell viability, increased apoptosis or autophagy in tumor cells, inhibition of migration and sphere formation (stemness), overcoming drug resistance (e.g., bortezomib resistance in myeloma), and downregulation of stemness markers such as CD44[2][3][4][5][7][10].
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