PP-22 promotes autophagy and apoptosis in the nasopharyngeal carcinoma cell line CNE-2 by inducing endoplasmic reticulum stress, downregulating STAT3 signaling, and modulating the MAPK pathway

J Cell Physiol. 2019 Mar;234(3):2618-2630. doi: 10.1002/jcp.27076. Epub 2018 Sep 7.

Abstract

Paris polyphylla var. yunnanensis, named Chong Lou, is considered an antitumor substance. In this study, we investigated the effect of PP-22, a monomer purified from P. polyphylla var. yunnanensis, on the nasopharyngeal carcinoma cell line CNE-2 in vitro. The results showed that PP-22 could inhibit the proliferation of CNE-2 cells via the induction of apoptosis, with evidence of the characteristic morphological changes in the apoptosis in the nucleus and an increase in Annexin V-positive cells. In addition, we found that PP-22 could activate the p38 mitogen-activated protein kinase (MAPK) pathway and that this activation was reversed by SB203580, a specific inhibitor of the p38 MAPK pathway. In contrast, PP-22 promoted apoptosis via an intrinsic pathway, including the endoplasmic reticulum stress pathway, in a caspase-dependent manner. A further study showed that PP-22 also induced apoptosis by downregulating the signal transducers and activators of transcription 3 (STAT3) pathway, and the inhibitory effect was also confirmed by STAT3 small interfering RNA. In addition, PP-22 could promote autophagy by inhibiting the extracellular regulated protein kinases (ERK) pathway. And autophagy plays a protective role against apoptosis. Together, these data show that PP-22 promotes autophagy and apoptosis in the nasopharyngeal carcinoma CNE-2 cell line.

Keywords: PP-22; apoptosis; autophagy; endoplasmic reticulum (ER) stress; mitogen-activated protein kinase (MAPK); signal transducers and activators of transcription 3 (STAT3).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Endoplasmic Reticulum Stress / drug effects*
  • Humans
  • Mitogen-Activated Protein Kinases / metabolism
  • Nasopharyngeal Carcinoma / drug therapy
  • Nasopharyngeal Neoplasms / drug therapy
  • Nasopharyngeal Neoplasms / genetics
  • STAT3 Transcription Factor / drug effects
  • STAT3 Transcription Factor / metabolism
  • Saponins / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Saponins
  • spirost-5-ene-3,17-diol 3-O-rhamnopyranosyl-(1-2)-glucopyranoside
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases