Caffeic acid phenethyl ester induces N-myc downstream regulated gene 1 to inhibit cell proliferation and invasion of human nasopharyngeal cancer cells

Kun Chun Chiang, Shih Wei Yang, Kai Ping Chang, Tsui Hsia Feng, Kang Shuo Chang, Ke Hung Tsui, Yi Syuan Shin, Chiu Chun Chen, Mei Chao, Horng Heng Juang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

24 Scopus citations

Abstract

Caffeic acid phenethyl ester (CAPE), a bioactive component extracted from propolis, is widely studied due to its anti-cancer effect. Nasopharyngeal carcinoma (NPC) is distinct from other head and neck carcinomas and has a high risk of distant metastases. N-myc downstream regulated gene 1 (NDRG1) is demonstrated as a tumor suppressor gene in several cancers. Our result showed that CAPE treatment could repress NPC cell growth, through induction of S phase cell cycle arrest, and invasion. CAPE treatment stimulated NDRG1 expression in NPC cells. NDRG1 knockdown increased NPC cell proliferation and invasion and rendered NPC cells less responsive to CAPE growth-inhibiting effect, indicating CAPE repressed NPC cell growth partly through NDRG1indcution. CAPE treatment increased phosphorylation of ERK, JNK, and p38 in a dose- and time-dependent manner. Pre-treatments by inhibitors of ERK (PD0325901), JNK (SP600125), or p38 (SB201290), respectively, all could partly inhibit the CAPE effect on NDRG1 induction in NPC cells. Further, STAT3 activity was also repressed by CAPE in NPC cells. In summary, CAPE attenuates NPC cell proliferation and invasion by upregulating NDRG1 expression via MAPK pathway and by inhibiting phosphorylation of STAT3. Considering the poor prognosis of NPC patients with metastasis, CAPE could be a promising agent against NPC.

Original languageEnglish
Article number1397
JournalInternational Journal of Molecular Sciences
Volume19
Issue number5
DOIs
StatePublished - 08 05 2018

Bibliographical note

Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • CAPE
  • MAPK
  • NDRG1
  • Nasopharyngeal cancer
  • STAT3

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