[1] ZHANG Jin FANG Yu JIANG Yina LI Chen WU Xiangyang SHEN Guanghui XIAO Haijuan,.Curcumin Inhibits Malignant Phenotype of Triple Negative Breast Cancer Cells by Regulating Glucose Metabolism Reprogramming [J]. Modern Traditional Chinese Medicine, 2023, (06): 109-117. [doi: 10.13424/j.cnki.mtcm.2023.06.022]
Curcumin Inhibits Malignant Phenotype of Triple Negative Breast Cancer Cells by Regulating Glucose Metabolism Reprogramming
- Article number:
- 1672-0571(2023)06-0109-09
- Keywords:
- Key words:Triple negative breast cancer; Curcumin; Reprogramming of glucose metabolism; Proliferation; Migration; Apoptosis
- ZTFLH:
- R271.1
- Code:
- A
- Abstract:
- Abstract：Objective To investigate the effects of curcumin on the proliferation, migration and apoptosis of triple negative breast cancer (TNBC) cells, and to elucidate its mechanism from the perspective of changes in key targets of glucose metabolism reprogramming. Methods Cell Counting Kit 8 (CCK-8 method) and Transwell method were used to detect the effects of curcumin on the proliferation, migration, and invasion of TNBC cells MDA-MB-231 (MB-231). Flow cytometry and Western blot (WB) were used to detect the effects of curcumin on apoptosis and cell cycle arrest in MB-231 cells. Real Time Quantitative Polymerase Chain Reaction (RT qPCR) and WB methods were used to detect the regulatory effects of curcumin on key targets of glucose metabolism reprogramming. Results The results showed that curcumin dose-dependently inhibited the proliferation and migration of MB-231 cells, significantly increased cell apoptosis, and led to S-phase arrest. At the same time, it also downregulated the mRNA expression of key targets for glucose metabolism reprogramming in MB-231 cells. The WB results showed that curcumin also downregulated the expression of anti apoptotic protein (Bcl-2) and key proteins for glucose metabolism reprogramming, and increased the expression of pro apoptotic related proteins (Cleared Caspase3, Bax). Conclusion Curcumin can significantly inhibit the proliferation and migration of MB-231 cells, and promote their apoptosis. The mechanism may be related to down-regulation of Bcl-2/Bax protein expression, induction of tumor cell apoptosis, down-regulation of aerobic glycolysis in breast cancer, and regulation of glycometabolism reprogramming in breast cancer.
References:
［1］Sung H,Ferlay J,Siegel RL,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］.CA:A Cancer Journal for Clinicians,2021,71(3):209-249.
［2］Peddi PF,Ellis MJ,Ma C.Molecular basis of triple negative breast cancer and implications for therapy［J］.International Journal of Breast Cancer,2012,2012:217185.
［3］Wahba HA,El-Hadaad HA.Current approaches in treatment of triple-negative breast cancer［J］.Cancer Biology & Medicine,2015,12(2):106-116.
［4］Hanahan D,Weinberg RA.Hallmarks of cancer:the next generation［J］.Cell,2011,144(5):646-674.
［5］ONeal J,Clem A,Reynolds L,et al.Inhibition of 6-phosphofructo-2-kinase (PFKFB3) suppresses glucose metabolism and the growth of HER2+ breast cancer［J］.Breast Cancer Research and Treatment,2016,160(1):29-40.
［6］Wang GN,Xu ZL,Wang CH,et al.Differential phosphofructokinase-1 isoenzyme patterns associated with glycolytic efficiency in human breast cancer and paracancer tissues［J］.Oncology Letters,2013,6(6):1701-1706.
［7］Fu DY,He CL,Wei JL,et al.PGK1 is a potential survival biomarker and invasion promoter by regulating the HIF-1α-mediated epithelial-mesenchymal transition process in breast cancer［J］.Cellular Physiology and Biochemistry:International Journal of Experimental Cellular Physiology,Biochemistry,and Pharmacology,2018,51(5):2434-2444.
［8］Giordano A,Tommonaro G.Curcumin and cancer［J］.Nutrients,2019,11(10):2376.
［9］刘小平,王劲进,王铭远,等.姜黄素逆转卵巢癌细胞紫杉醇耐药的机制研究［J］.湖南师范大学学报(医学版),2021,18(3):109-113.
［10］张凤娟.糖代谢机制在丹参酮ⅡA和姜黄素抑制食管癌细胞增殖的作用研究［D］.北京:北京工业大学,2016.
［11］Shen H,Perez RE,Davaadelger B,et al.Two 4N cell-cycle arrests contribute to cisplatin-resistance［J］.PLoS One,2013,8(4):e59848.from 86 studies［J］.Journal of Cancer Research and Clinical Oncology,2019,145(4):967-999.
［12］Yu M，Chen S，Hong W，et al.Prognostic role of glycolysis for cancer outcome：evidence from 86 studies［J］.Journal of cancer research and clinical oncology,2019,145(4)：967-999.
［13］Gomez LS,Zancan P,Marcondes MC,et al.Resveratrol decreases breast cancer cell viability and glucose metabolism by inhibiting 6-phosphofructo-1-kinase［J］.Biochimie,2013,95(6):1336-1343.
［14］苗淑涵,高晋生.姜黄素药理作用的研究进展［J］.光明中医,2017,32(15):2284-2287.
［15］吴山,戚益铭,胡林峰.姜黄素抗肿瘤作用及机制研究进展［J］.生物技术世界,2014,11(7):124-125.
［16］Giridhar KV,Liu MC.Available and emerging molecular markers in the clinical management of breast cancer［J］.Expert Review of Molecular Diagnostics,2019,19(10):919-928.
［17］Park H,Chang SK,Kim JY,et al.Risk factors for distant metastasis as a primary site of treatment failure in early-stage breast cancer［J］.Chonnam Medical Journal,2014,50(3):96-101.
［18］李新,牛冰,李庆辉,等.姜黄素联合KLF8基因siRNA调控JAK2/STAT3信号通路对乳腺癌细胞生长抑制作用的研究［J］.安徽医科大学学报,2019,54(1):69-73.
［19］Ramachandran C,Rodriguez S,Ramachandran R,et al.Expression profiles of apoptotic genes induced by curcumin in human breast cancer and mammary epithelial cell lines［J］.Anticancer Research,2005,25(5):3293-3302.
［20］Czabotar PE,Lessene G,Strasser A,et al.Control of apoptosis by the BCL-2 protein family:implications for physiology and therapy［J］.Nature Reviews Molecular Cell Biology,2014,15(1):49-63.
［21］Zhai DY,Jin CF,Huang ZW,et al.Differential regulation of Bax and Bak by anti-apoptotic Bcl-2 family proteins Bcl-B and Mcl-1［J］.The Journal of Biological Chemistry,2008,283(15):9580-9586.
［22］Xin MG,Deng XM.Nicotine inactivation of the proapoptotic function of bax through phosphorylation［J］.The Journal of Biological Chemistry,2005,280(11):10781-10789.
［23］Cao G,Minami M,Pei W,et al.Intracellular Bax translocation after transient cerebral ischemia:implications for a role of the mitochondrial apoptotic signaling pathway in ischemic neuronal death［J］.Journal of Cerebral Blood Flow and Metabolism:Official Journal of the International Society of Cerebral Blood Flow and Metabolism,2001,21(4):321-333.
［24］Fujimura M,Morita-Fujimura Y,Kawase M,et al.Manganese superoxide dismutase mediates the early release of mitochondrial cytochrome C and subsequent DNA fragmentation after permanent focal cerebral ischemia in mice［J］.The Journal of Neuroscience:the Official Journal of the Society for Neuroscience,1999,19(9):3414-3422.
［25］Oliva A,Rosebrock A,Ferrezuelo F,et al.The cell cycle-regulated genes of Schizosaccharomyces pombe［J］.PLoS Biology,2005,3(7):e225.
［26］Varna M,Lehmann-Che J,Turpin E,et al.p53 dependent cell-cycle arrest triggered by chemotherapy in xenografted breast tumors［J］.International Journal of Cancer,2009,124(4):991-997.
［27］Du Y,Wei N,Ma RL,et al.A miR-210-3p regulon that controls the Warburg effect by modulating HIF-1α and p53 activity in triple-negative breast cancer［J］.Cell Death & Disease,2020,11(9):731.
［28］Xiao Y,Ma D,Yang YS,et al.Comprehensive metabolomics expands precision medicine for triple-negative breast cancer［J］.Cell Research,2022,32(5):477-490.
［29］Lai YW,Hsu WJ,Lee WY,et al.Prognostic value of a glycolytic signature and its regulation by Y-box-binding protein 1 in triple-negative breast cancer［J］.Cells,2021,10(8):1890.
［30］Wu Q,ba-alawi W,Deblois G,et al.GLUT1 inhibition blocks growth of RB1-positive triple negative breast cancer［J］.Nature Communications,2020,11:4205.
［31］Coelho RG,Calaa IC,Celestrini DM,et al.Hexokinase and phosphofructokinase activity and intracellular distribution correlate with aggressiveness and invasiveness of human breast carcinoma［J］.Oncotarget,2015,6(30):29375-29387.
［32］Peng F,Li Q,Sun JY,et al.PFKFB3 is involved in breast cancer proliferation,migration,invasion and angiogenesis［J］.International Journal of Oncology,2018,52(3):945-954.
［33］Li Z,Yang LN,Zhang S,et al.Valproic acid suppresses breast cancer cell growth through triggering pyruvate kinase M2 isoform mediated Warburg effect［J］.Cell Transplantation,2021,30:9636897211027524.
［34］Krzeslak A,Wojcik-Krowiranda K,Forma E,et al.Expression of GLUT1 and GLUT3 glucose transporters in endometrial and breast cancers［J］.Pathology & Oncology Research,2012,18(3):721-728.
Memo
基金项目：陕西中医药大学创新团队建设项目（2019-YL06）