Polyphyllin II Induces Protective Autophagy and Apoptosis via Inhibiting PI3K/AKT/mTOR and STAT3 Signaling in Colorectal Cancer Cells

Jun Kui Li, Hai Tao Sun, Xiao Li Jiang, Yi Fei Chen, Zhu Zhang, Ying Wang, Wen Qing Chen, Zhang Zhang, Stephen Cho Wing Sze, Pei Li Zhu*, Ken Kin Lam Yung*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Polyphyllin II (PPII) is a natural steroidal saponin occurring in Rhizoma Paridis. It has been demonstrated to exhibit anti-cancer activity against a variety of cancer cells. However, the anti-colorectal cancer (CRC) effects and mechanism of action of PPII are rarely reported. In the present study, we showed that PPII inhibited the proliferation of HCT116 and SW620 cells. Moreover, PPII induced G2/M-phase cell cycle arrest and apoptosis, as well as protective autophagy, in CRC cells. We found that PPII-induced autophagy was associated with the inhibition of PI3K/AKT/mTOR signaling. Western blotting results further revealed that PPII lowered the protein levels of phospho-Src (Tyr416), phospho-JAK2 (Tyr1007/1008), phospho-STAT3 (Tyr705), and STAT3-targeted molecules in CRC cells. The overactivation of STAT3 attenuated the cytotoxicity of PPII against HCT116 cells, indicating the involvement of STAT3 inhibition in the anti-CRC effects of PPII. PPII (0.5 mg/kg or 1 mg/kg, i.p. once every 3 days) suppressed HCT116 tumor growth in nude mice. In alignment with the in vitro results, PPII inhibited proliferation, induced apoptosis, and lowered the protein levels of phospho-STAT3, phospho-AKT, and phospho-mTOR in xenografts. These data suggest that PPII could be a potent therapeutic agent for the treatment of CRC.

Original languageEnglish
Article number11890
JournalInternational Journal of Molecular Sciences
Volume23
Issue number19
DOIs
Publication statusPublished - 1 Oct 2022

User-Defined Keywords

  • apoptosis
  • autophagy
  • cell cycle arrest
  • colorectal cancer
  • PI3K/AKT/mTOR
  • polyphyllin II
  • STAT3

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