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

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 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.

Novel pentacyclic derivatives and benzylidenes of the progesterone series cause anti-estrogenic and antiproliferative effects and induce apoptosis in breast cancer cells

“…Cyclin D1 was analyzed to be an important ERα-dependent gene and cell cycle regulator (Fig. 3 B) [ 58 , 59 ]. A decrease in ERα expression and PARP cleavage in MCF7 cells were accompanied by a slight decrease in cyclin D1 expression at a concentration of 15 µM when fulvestrant treatment did not affect cyclin D1 expression.…”

Signaling Pathways and Natural Compounds in Triple-Negative Breast Cancer Cell Line

“…The research suggested curcumin as a potential anti-TNBC due to its ability to promote apoptosis, and to block the cell cycle of TNBC cells (MDA-MB-231) by inhibiting restoring DLC1 and EZH2 expression; it also inhibited the migration, invasion, and proliferation in vitro and in vivo studies with an IC 50 value at 40 µM for both MDA-MB-231 and MDA-MB-468 cell lines [191]. Other research showed that curcumin inhibited the SIK3-mediated cyclin D upregulation in the G1/S cell cycle and inhibited cell growth during epithelial-mesenchymal transition (EMT), with an IC 50 value of 25 µM in the MDA-MB-231 cell line by in vitro and in vivo studies [192].…”

Curcumin and its Analogs and Carriers: Potential Therapeutic Strategies for Human Osteosarcoma

“…Curcumin mediates its promising activities by regulating several key molecular targets. They include (1) transcription factors [e.g., activator protein (AP)-1, β-catenin, NF-κB, peroxisome proliferator-activated receptor (PPAR)-γ, and signal transducer and activator of transcription (STAT)] [1, 2, 9, [19][20][21][22], (2) enzymes [e.g., cyclooxygenase (COX)2, 5-lipoxygenase (LOX), heme oxygenase-1 (HO-1), and inducible nitric oxide synthase (iNOS)] [1,2,9,19,20,23,24], (3) protein kinases [mitogen-activated protein kinases (MAPKs), Janus kinase (JAK), adenosine monophosphateactivated protein kinase (AMPK), protein kinase A (PKA), and PKC [2, 9, 19-22, 24, 25], (4) cell cycle proteins (e.g., cyclin D1 and E) [1,2,9,[19][20][21]25], (5) cytokines [e.g., tumor necrosis factor (TNF), interleukins (ILs)-1 and 6, and chemokines] [1,2,20], (6) receptors [e.g., epidermal growth factor receptor (EGFR) and human EGFR (HER)2)] [2,9,19,20,23], (7) cell surface adhesion molecules [e.g., intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and endothelial leukocyte adhesion molecule (ELAM)-1 [2,20], and (8) genes that regulate cell proliferation and apoptosis (e.g., p21, p27, and p53) [1,2,9,[19]…”