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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
Author(s) -
Tan GuiXiang,
Wang XinNing,
Tang YunYun,
Cen WanJing,
Li ZhenHua,
Wang GuoCai,
Jiang JianWei,
Wang XiCheng
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27076
Subject(s) - apoptosis , microbiology and biotechnology , autophagy , p38 mitogen activated protein kinases , endoplasmic reticulum , mapk/erk pathway , kinase , unfolded protein response , signal transduction , annexin , stat3 , protein kinase a , cell culture , nasopharyngeal carcinoma , chemistry , biology , biochemistry , medicine , genetics , radiation therapy
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.