The Antitumor Effect of Caffeic Acid Phenethyl Ester by Downregulating Mucosa-Associated Lymphoid Tissue 1 via AR/p53/NF-κB Signaling in Prostate Carcinoma Cells

Kang Shuo Chang, Ke Hung Tsui, Shu Yuan Hsu, Hsin Ching Sung, Yu Hsiang Lin, Chen Pang Hou, Pei Shan Yang, Chien Lun Chen, Tsui Hsia Feng, Horng Heng Juang

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Caffeic acid phenethyl ester (CAPE), a honeybee propolis-derived bioactive ingredient, has not been extensively elucidated regarding its effect on prostate cancer and associated mechanisms. The mucosa-associated lymphoid tissue 1 gene (MALT1) modulates NF-κB signal transduction in lymphoma and non-lymphoma cells. We investigated the functions and regulatory mechanisms of CAPE in relation to MALT1 in prostate carcinoma cells. In p53-and androgen receptor (AR)-positive prostate carcinoma cells, CAPE downregulated AR and MALT1 expression but enhanced that of p53, thus decreasing androgen-induced activation of MALT1 and prostate-specific antigen expressions. p53 downregulated the expression of MALT in prostate carcinoma cells through the putative consensus and nonconsensus p53 response elements. CAPE downregulated MALT1 expression and thus inhibited NF-κB activity in p53-and AR-negative prostate carcinoma PC-3 cells, eventually reducing cell proliferation, invasion, and tumor growth in vitro and in vivo. CAPE induced the ERK/JNK/p38/AMPKα1/2 signaling pathways; however, pretreatment with the corresponding inhibitors of MAPK or AMPK1/2 did not inhibit the CAPE effect on MALT1 blocking in PC-3 cells. Our findings verify that CAPE is an effective antitumor agent for human androgen dependent and-independent prostate carcinoma cells in vitro and in vivo through the inhibition of MALT1 expression via the AR/p53/NF-κB signaling pathways.

Original languageEnglish
Article number274
JournalCancers
Volume14
Issue number2
DOIs
Publication statusPublished - Jan 2022

Keywords

  • AR
  • BTG2
  • CAPE
  • MALT1
  • NDRG1
  • NF-κB
  • P53
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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