Quercetin suppresses the mobility of breast cancer by suppressing glycolysis through Akt-mTOR pathway mediated autophagy induction
Authors: Ying Zan
Xiaoran Yin
Shan Huang
Lili Han
Lijun Jia
Ya Guo
Journal: Life Sciences (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Akt-mTOR pathway; Autophagy; Breast Cancer; Glycolysis; Quercetin.
Affiliations: Department of oncology, the Second Affiliated Hospital, Xi'an Jiao Tong University,Shaanxi 646000, China. Electronic address: ., Department of oncology, the Second Affiliated Hospital, Xi'an Jiao Tong University,Shaanxi 646000, China.

Abstract:  Tumor metastasis is the primary factor causing death of cancer patients and it is a study emphasis in cancer treatment to suppress tumor metastasis by inhibiting glycolysis, which is the main way of energy supply for cell mobility in tumor. In the present study, we aimed to explore the effect of quercetin, a bioactive flavonoid, on tumor metastasis and cell glycolysis and its related functionary mechanism in breast cancer progression. Firstly, trans-well invasion assay and wound healing assay indicated that quercetin effectively suppressed cell mobility. The corresponding western blot revealed that quercetin treatment down-regulated the expression of cell migration marker proteins, such as matrix metalloproteinase 2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF). The further experiments exhibited that quercetin successfully blocked cell glycolysis by inhibiting the level of glucose uptake and the production of lactic acid, and also decreased the level of glycolysis-related proteins Pyruvate kinase M2 (PKM2), Glucose transporter1(GLUT1) and Lactate dehydrogenase A (LDHA). The above results revealed that quercetin might inhibit glycolysis to limit the migration of tumor cells by reducing the acidity of the tumor microenvironment. Moreover, our further investigation showed that quercetin induced obvious autophagy via inactivating the Akt-mTOR pathway. At the same time, the application of autophagy inhibitor 3-MA and Akt-mTOR pathway inducer IGF-1 further demonstrated that quercetin exerted inhibiting effect on cell mobility and glycolysis through Akt-mTOR pathway mediated autophagy induction. At last, the in vivo experiments also showed that quercetin treatment could suppress tumor growth and metastasis, inhibit glycolysis and induce autophagy through the inhibition of p-AKT/AKT. Taken together, we firstly revealed that quercetin suppressed the progression of breast cancer by inhibiting cell mobility and glycolysis through Akt-mTOR pathway mediated autophagy induction and may provide a potential therapeutic target for breast cancer treatment. 

Retracted: No

PubPeer comments:
 Figure1C.  Quercetin suppressed cell invasion and migration of breast cancer. ... C. Transwell invasion assay was employed to value cell invasion ability. The number of invasion cells in per field was analyzed. Two points of interest here. First, the Quercetin 30-u00b5M panels are the same for the two cell lines, apart from a 90-deg rotation and the addition of some cells (yellow boxes). ![file] Second, the two Control panels also overlap after a 180-deg flip. ![file] In fact both overlap with Fig 1C from [Tian et al (2018)] .  SGC-7901 and MGC-803 cells were transfected with miR-361-5p mock or miR-361-5p mimic respectively. ... (C-D) Invasion ability of transfected cells were measured by transwell model. ![] And Fig 2B from [Yang et al (2018)] .  HOTAIR promotes invasion and migration of HCC cells through enhancing EMT. Huh7 cells were transfected with pcDNA3.1-HOTAIR or scramble RNA respectively. ... (B-C) Invasion ability of cells was compared using Transwell model. ![] ...and many other manifestations. A case could be made that all three papers are productions from a papermill, with possible cases listed in a Google spreadsheet. https: docs.google.com spreadsheets d 19wUtpXazLg2zKbTpDBuq0smG6-A7VHYifkieoyyuTcQ edit?usp=sharing , 
 Fig 2C. These styled Western Blots, resembling rows of processionary caterpillars crawling across a background texture with occasional repeated segments, are another distinctive feature of this corpus. ![file] , 
 From the left: - Fig 5C from  Silencing of H19 inhibits the adipogenesis and inflammation response in ox-LDL-treated Raw264.7 cells by up-regulating miR-130b ([han et al 2018] ); - **Fig 3A**; - Fig 3B from  Emodin Inhibits Colon Cancer Cell Invasion and Migration by Suppressing Epithelialu2010Mesenchymal Transition via the Wnt u03b2-Catenin Pathway ([Gu et al 2019] ). ![file] Unexpectedly similar band. ,