Curcumin-induced antitumor effects on triple-negative breast cancer patient-derived xenograft tumor mice through inhibiting salt-induced kinase-3 protein

Tzu Chun Cheng, John Oliver Sayseng, Shih Hsin Tu, Ting Ching Juan, Chia Lang Fang, You Cheng Liao, Cheng Ying Chu, Hui Wen Chang, Yun Yen, Li Ching Chen, Yuan Soon Ho

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

This study demonstrated for the first time that curcumin effectively inhibits the growth of triple-negative breast cancer (TNBC) tumors by inhibiting the expression of salt-induced kinase-3 (SIK3) protein in patient-derived xenografted tumor mice (TNBC-PDX). For TNBC patients, chemotherapy is the only option for postoperative adjuvant treatment. In this study, we detected the SIK3 mRNA expression in paired-breast cancer tissues by qPCR analysis. The results revealed that SIK3 mRNA expression was significantly higher in tumor tissues when compared to the normal adjacent tissues (73.25 times, n = 183). Thus, it is proposed for the first time that the antitumor effect induced by curcumin by targeting SIK3 can be used as a novel strategy for the therapy of TNBC tumors. In vitro mechanism studies have shown that curcumin (>25 mM) inhibits the SIK3-mediated cyclin D upregulation, thereby inhibiting the G1/S cell cycle and arresting TNBC (MDA-MB-231) cancer cell growth. The SIK3 overexpression was associated with increased mesen-chymal markers (i.e., Vimentin, a-SMA, MMP3, and Twist) during epithelialemesenchymal transition (EMT). Our results demonstrated that curcumin inhibits the SIK3-mediated EMT, effectively attenuating the tumor migration. For clinical indications, dietary nutrients (such as curcumin) as an adjuvant to chemotherapy should be helpful to TNBC patients because the current trend is to shrink the tumor with preoperative chemotherapy and then perform surgery. In addition, from the perspective of chemoprevention, curcumin has excellent clinical application value.

Original languageEnglish
Article number6
Pages (from-to)622-637
Number of pages16
JournalJournal of Food and Drug Analysis
Volume29
Issue number4
DOIs
Publication statusPublished - 2021

Keywords

  • Curcumin
  • Epithelial-mesenchymal transition
  • Patient-derived xenografted mice
  • Salt-induced kinase-3
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Food Science
  • Pharmacology

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