RETRACTED: Ursolic Acid Exhibits Potent Anticancer Effects in Human Metastatic Melanoma Cancer Cells (SK-MEL-24) via Apoptosis Induction, Inhibition of Cell Migration and Invasion, Cell Cycle Arrest, and Inhibition of Mitogen-Activated Protein Kinase (MAPK)/ERK Signaling Pathway (Retracted Article)

被引:25
作者
Liu, Pengcheng [1 ,2 ]
Du, Ruili [3 ]
Yu, Xin [1 ,2 ]
机构
[1] Jilin Univ, Dept Hand & Pediat Surg, Hosp 1, Changchun, Jilin, Peoples R China
[2] Jilin Prov Key Lab Tissue Repair Reconstruct & Re, Changchun, Jilin, Peoples R China
[3] Second Hosp Changchun City, Dept Clin Lab Med, Changchun, Jilin, Peoples R China
来源
MEDICAL SCIENCE MONITOR | 2019年 / 25卷
关键词
Apoptosis; Apoptosis Inducing Factor; Cell Cycle; Flow Cytometry; gp100 Melanoma Antigen; TRITERPENOIDS; DISCOVERY;
D O I
10.12659/MSM.913069
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background: Ursolic acid is an important bioactive triterpenoid that has been reported to be of tremendous pharmacolog-ical importance. However, the anticancer potential of ursolic acid has not been examined against metastatic melanoma cells. Therefore, in this study we examined the anticancer potential of ursolic acid and its mode of action. Material/Method: WST-1 and colony formation assays were used for cell viability assessment. Cell cycle analysis was performed by flow cytometry. Apoptosis was detected by AO/EB staining using fluorescence microscopy. Cell migration and invasion were assessed by Boyden chamber assay. Protein expression was checked by Western blotting. Results: The results revealed that ursolic acid exerts significant (p<0.01) growth-inhibitory effects on SK-MEL-24 cells. The IC50 of ursolic acid against SK-MEL-24 cells was 25 mu M. Our investigation of the underlying mechanism revealed that ursolic acid prompts apoptotic cell death of the SK-MEL-24 cells, which was linked with increased expression of Bax and Caspase 3 and 9, and decreased expression of BcI-2. Ursolic acid also halted the SKMEL-24 cells at GO/G1 phase of the cell cycle and also downregulated the expression of Cyclin B1 and Cdc25. Ursolic acid significantly (p<0.01) inhibited the migration and invasion of SK-MEL-2 cells, indicative of its anti-metastatic potential. Finally, ursolic acid inhibited the MAPK/ERK pathway by suppressing the expression of p-P38 and p-ERK. Conclusions: Ursolic acid appears to be a potent molecule for the treatment of melanoma.
引用
收藏
页码:1283 / 1290
页数:8
相关论文
共 17 条
  • [1] Circulating Tumor Cell Clusters Are Oligoclonal Precursors of Breast Cancer Metastasis
    Aceto, Nicola
    Bardia, Aditya
    Miyamoto, David T.
    Donaldson, Maria C.
    Wittner, Ben S.
    Spencer, Joel A.
    Yu, Min
    Pely, Adam
    Engstrom, Amanda
    Zhu, Huili
    Brannigan, Brian W.
    Kapur, Ravi
    Stott, Shannon L.
    Shioda, Toshi
    Ramaswamy, Sridhar
    Ting, David T.
    Lin, Charles P.
    Toner, Mehmet
    Haber, Daniel A.
    Maheswaran, Shyamala
    [J]. CELL, 2014, 158 (05) : 1110 - 1122
  • [2] Ajayi T. O., 2014, African Journal of Biomedical Research, V17, P165
  • [3] The Soft Agar Colony Formation Assay
    Borowicz, Stanley
    Van Scoyk, Michelle
    Avasarala, Sreedevi
    Rathinam, Manoj Kumar Karuppusamy
    Tauler, Jordi
    Bikkavilli, Rama Kamesh
    Winn, Robert A.
    [J]. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2014, (92):
  • [4] Natural Products as a Vital Source for the Discovery of Cancer Chemotherapeutic and Chemopreventive Agents
    Cragg, Gordon M.
    Pezzuto, John M.
    [J]. MEDICAL PRINCIPLES AND PRACTICE, 2016, 25 : 41 - 59
  • [5] Triterpenoids isolated from apple peels have potent antiproliferative activity and may be partially responsible for apple's anticancer activity
    He, Xiangjiu
    Liu, Rui Hai
    [J]. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2007, 55 (11) : 4366 - 4370
  • [6] Proliferative inhibition, cell-cycle dysregulation, and induction of apoptosis by ursolic acid in human non-small cell lung cancer A549 cells
    Hsu, YL
    Kuo, PL
    Lin, CC
    [J]. LIFE SCIENCES, 2004, 75 (19) : 2303 - 2316
  • [7] The secreted glycolytic enzyme GPI/AMF stimulates glioblastoma cell migration and invasion in an autocrine fashion but can have anti-proliferative effects
    Kathagen-Buhmann, Annegret
    Maire, Cecile L.
    Weller, Jonathan
    Schulte, Alexander
    Matschke, Jakob
    Holz, Mareike
    Ligon, Keith L.
    Glatzel, Markus
    Westphal, Manfred
    Lamszus, Katrin
    [J]. NEURO-ONCOLOGY, 2018, 20 (12) : 1594 - 1605
  • [8] Novel strategies for the discovery of plant-derived anticancer agents
    Kinghorn, AD
    Farnsworth, NR
    Soejarto, DD
    Cordell, GA
    Swanson, SM
    Pezzuto, JM
    Wani, MC
    Wall, ME
    Oberlies, NH
    Kroll, DJ
    Kramer, RA
    Rose, WC
    Vite, GD
    Fairchild, CR
    Peterson, RW
    Wild, R
    [J]. PHARMACEUTICAL BIOLOGY, 2003, 41 : 53 - 67
  • [9] The Safety of Artemisinin Derivatives for the Treatment of Malaria in the 2nd or 3rd Trimester of Pregnancy: A Systematic Review and Meta-Analysis
    Kovacs, Stephanie D.
    van Eijk, Anna Maria
    Sevene, Esperanca
    Dellicour, Stephanie
    Weiss, Noel S.
    Emerson, Scott
    Steketee, Richard
    ter Kuile, Feiko O.
    Stergachis, Andy
    [J]. PLOS ONE, 2016, 11 (11):
  • [10] The investigational Aurora kinase A inhibitor alisertib (MLN8237) induces cell cycle G2/M arrest, apoptosis, and autophagy via p38 MAPK and Akt/mTOR signaling pathways in human breast cancer cells
    Li, Jin-Ping
    Yang, Yin-Xue
    Liu, Qi-Lun
    Pan, Shu-Ting
    He, Zhi-Xu
    Zhang, Xueji
    Yang, Tianxin
    Chen, Xiao-Wu
    Wang, Dong
    Qiu, Jia-Xuan
    Zhou, Shu-Feng
    [J]. DRUG DESIGN DEVELOPMENT AND THERAPY, 2015, 9 : 1627 - 1652