OncoTargets and Therapy (Aug 2020)
Cryptanshinone Inhibits the Glycolysis and Inhibits Cell Migration Through PKM2/β-Catenin Axis in Breast Cancer
Abstract
Jiefeng Zhou,1,2,* Chih-Ming Su,3,4,* Hsin-An Chen,3,4 Shicong Du,2 Chang-Wei Li,5 Haoran Wu,2 Shin-Han Tsai,6 Yu-Ting Yeh1,7 1Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei City, Taiwan; 2Ningbo AJcore Biosciences Inc, High-tech Zone, Ningbo City, People’s Republic of China; 3Division of General Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan; 4Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; 5Ningbo AllBiolife Biotech Inc, High-tech Zone, Ningbo City, People’s Republic of China; 6Department of Emergency Medicine, Shuang Ho Hospital, Taipei Medical University, Institute of Injury Prevention and Control, Taipei Medical University, Taipei City, Taiwan; 7Information Technology Office, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan*These authors contributed equally to this workCorrespondence: Yu-Ting YehInformation Technology Office, Shuang Ho Hospital, Taipei Medical University, New Taipei City, TaiwanTel +886 22490088 Ext 8901Email [email protected]: Breast cancer is one of the most prevalent gynecologic malignancies worldwide. Despite the high sensitivity in response to chemotherapy, drug resistance occurred frequently in clinical treatment. Cryptotanshinone (CTS) is a herbal medicine and has been identified as an anti-inflammatory and anti-oxidative drug.Methods: In vitro assays, including the cell proliferation assay, colony formation assay, Western blot analysis, transwell migration/invasion assays, and cell scratch assay were used to explore the biological activities and working mechanism of CTS. Breast cancer cells were also transfected with PKM2 expressing vectors to define the molecular mechanisms involved in CTS-mediated anti-tumor activity.Results: We found that CTS shows anti-proliferative effects and decreases the clonogenic ability of breast cancer cells. We also found that CTS inhibited the migration and invasion activity of MCF-7 and MDA-MB-231 cells by different analyzed methods. CTS also downregulated the levels of glycolysis-related proteins, such as PKM2, LDHA, and HK2. In addition, overexpression of PKM2 recovered CTS-mediated suppression of cell proliferation, colony formation, and cell mobility of breast cancer cells. We also found PKM2 was significantly overexpressed in tumor tissues and invasive ductal breast carcinoma compared to normal tissues and patients with high PKM2 expression had worse overall survival and metastasis-free survival outcomes.Conclusion: CTS inhibited the proliferation, migration, and invasion of breast cancer cells. The involved mechanism may refer to the downregulation of the PKM2/β-catenin axis.Keywords: cryptotanshinone, glycolysis, breast cancer, PKM2, migration
