Polyphenols Extracted from Artemisia annua L. Exhibit Anti-Cancer Effects on Radio-Resistant MDA-MB-231 Human Breast Cancer Cells by Suppressing Stem Cell Phenotype, β-Catenin, and MMP-9

Molecules

HyeJung Kim¹  YoungShin Ko¹  ChoongWon Kim²  EunJoo Jung²  WonSup Lee³  Se-il Go³  Jin-Myung Jung⁴  BaeKwon Jeong⁵  SoonChan Hong⁶  GonSup Kim⁷ 

[1] Department of Pharmacology, College of Medicine, Institute of Health Sciences, Gyeongsang National University, 816 Beongil 15 Jinjudaero, Jinju 52727, Korea;Departments of Biochemistry, Institute of Health Sciences, Gyeongsang National University College of Medicine, 90 Chilam-dong, Jinju 660-702, Korea;Departments of Internal Medicine, Institute of Health Sciences and Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, 90 Chilam-dong, Jinju 660-702, Korea;Departments of Neurosurgery, Institute of Health Sciences and Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, 90 Chilam-dong, Jinju 660-702, Korea;Departments of Radiation Oncology, Institute of Health Sciences and Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, 90 Chilam-dong, Jinju 660-702, Korea;Departments of Surgery, Institute of Health Sciences and Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, 90 Chilam-dong, Jinju 660-702, Korea;School of Veterinary and Institute of Life Science, Gyeongsang National University, 900 Gajwadong, Jinju 660-701, Korea;

关键词: breast cancer cells;    polyphenols;    Artemisia annua L.;    stem cells;    EMT;   

DOI  :  10.3390/molecules25081916

来源: DOAJ

【 摘 要 】

Artemisia annua L. has been reported to show anti-cancer activities. Here, we determined whether polyphenols extracted from Artemisia annua L. (pKAL) exhibit anti-cancer effects on radio-resistant MDA-MB-231 human breast cancer cells (RT-R-MDA-MB-231 cells), and further explored their molecular mechanisms. Cell viability assay and colony-forming assay revealed that pKAL inhibited cell proliferation on both parental and RT-R-MDA-MB-231 cells in a dose-dependent manner. The anti-proliferative effects of pKAL on RT-R-MDA-MB-231 cells were superior or similar to those on parental ones. Western blot analysis revealed that expressions of cluster of differentiation 44 (CD44) and Oct 3/4, matrix metalloproteinase-9 (MMP-9) and signal transducer and activator of transcription-3 (STAT-3) phosphorylation were significantly increased in RT-R-MDA-MB-231 cells compared to parental ones, suggesting that these proteins could be associated with RT resistance. pKAL inhibited the expression of CD44 and Oct 3/4 (CSC markers), and β-catenin and MMP-9 as well as STAT-3 phosphorylation of RT-R-MDA-MB-231. Regarding upstream signaling, the JNK or JAK2 inhibitor could inhibit STAT-3 activation in RT-R-MDA-MB-231 cells, but not augmented pKAL-induced anti-cancer effects. These findings suggest that c-Jun N-terminal kinase (JNK) or Janus kinase 2 (JAK2)/STAT3 signaling are not closely related to the anti-cancer effects of pKAL. In conclusion, this study suggests that pKAL exhibit anti-cancer effects on RT-R-MDA-MB-231 cells by suppressing CD44 and Oct 3/4, β-catenin and MMP-9, which appeared to be linked to RT resistance of RT-R-MDA-MB-231 cells.

【 授权许可】

Unknown