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

Authors

Tzu-Chun Cheng, School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
John Oliver Sayseng, International Graduate Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
Shih-Hsin Tu, Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan
Ting-Ching Juan, School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
Chia-Lang Fang, Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
You-Cheng Liao, Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
Cheng-Ying Chu, TMU Research Center of Cancer Translational Medicine, Taipei Medical University; Taipei, Taiwan
Hui-Wen Chang, Department of Medical Laboratory, Taipei Medical University Hospital, Taipei, Taiwan
Yun Yen, TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan
Li-Ching Chen, TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, TaiwanFollow
Yuan-Soon Ho, Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, TaiwanFollow

Keywords

curcumin, epithelial-mesenchymal transition, patient-derived xenografted mice, salt-induced kinase-3, triple-negative breast cancer

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 PCR 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 μM) 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 mesenchymal markers (i.e., Vimentin, α-SMA, MMP3, and Twist) during epithelial-mesenchymal 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.

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Recommended Citation

Cheng, Tzu-Chun; Sayseng, John Oliver; Tu, Shih-Hsin; Juan, Ting-Ching; Fang, Chia-Lang; Liao, You-Cheng; Chu, Cheng-Ying; Chang, Hui-Wen; Yen, Yun; Chen, Li-Ching; and Ho, Yuan-Soon (2021) "Curcumin-induced antitumor effects on triple-negative breast cancer patient-derived xenograft tumor mice through inhibiting salt-induced kinase-3 protein," Journal of Food and Drug Analysis: Vol. 29 : Iss. 4 , Article 6.
Available at: https://doi.org/10.38212/2224-6614.3387

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