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Bisdemethoxycurcumin Promotes Apoptosis and Inhibits the Epithelial–Mesenchymal Transition through the Inhibition of the G-Protein-Coupled Receptor 161/Mammalian Target of Rapamycin Signaling Pathway in Triple Negative Breast Cancer Cells
- Source :
- Journal of Agricultural and Food Chemistry. 69:14557-14567
- Publication Year :
- 2021
- Publisher :
- American Chemical Society (ACS), 2021.
-
Abstract
- Triple negative breast cancer (TNBC) is one of the leading causes of cancer death in the world and lacks an effective targeted therapy. G-protein-coupled receptor 161 (GPR161) has been demonstrated to perform the functional regulations on TNBC progression and might be a potential new target for TNBC therapy. This study showed the effects of bisdemethoxycurcumin (BDMC) on GPR161 regulation, indicating that BDMC effectively inhibited GPR161 expression and downregulated GPR161-driven signaling. BDMC showed the potent inhibitory effects on TNBC proliferation through suppressing GPR161-mediated mammalian target of rapamycin (mTOR)/70 kDa ribosomal protein S6 kinase (p70S6K) activation. Besides, in this study, we discover the mechanism of GPR161-driven TNBC metastasis, linking to GPR161-mediated twist-related protein 1 (Twist1)/matrix metallopeptidase 9 (MMP9) contributing to the epithelial-mesenchymal transition (EMT). BDMC effectively repressed GPR161-mediated TNBC metastasis via inhibiting Twist1/MMP9-induced EMT. The three-dimensional invasion assay also showed that BDMC significantly inhibited TNBC invasion. The combination treatment of BDMC and rapamycin enhanced the inhibition of TNBC proliferation and metastasis through increasing the blockage of mTOR activation. Furthermore, this study also observed that BDMC activated the caspase 3/9 signaling pathway to induce TNBC apoptosis. Therefore, BDMC could be applicable to anticancer therapy, especially targeting on the GPR161-driven cancer type.
- Subjects :
- Epithelial-Mesenchymal Transition
Apoptosis
Triple Negative Breast Neoplasms
MMP9
Receptors, G-Protein-Coupled
Metastasis
chemistry.chemical_compound
Cell Movement
Diarylheptanoids
Cell Line, Tumor
Bisdemethoxycurcumin
medicine
Humans
Epithelial–mesenchymal transition
Triple-negative breast cancer
PI3K/AKT/mTOR pathway
Cell Proliferation
Sirolimus
Chemistry
TOR Serine-Threonine Kinases
General Chemistry
medicine.disease
Gene Expression Regulation, Neoplastic
Ribosomal protein s6
Cancer research
Signal transduction
General Agricultural and Biological Sciences
Signal Transduction
Subjects
Details
- ISSN :
- 15205118 and 00218561
- Volume :
- 69
- Database :
- OpenAIRE
- Journal :
- Journal of Agricultural and Food Chemistry
- Accession number :
- edsair.doi.dedup.....8363bf6805220c699d686facc3eb72b2