Polyphenols Extracted from <i>Artemisia annua</i> 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
Young Shin Ko,
Eun Joo Jung,
Se-il Go,
Bae Kwon Jeong,
Gon Sup Kim,
Jin-Myung Jung,
Soon Chan Hong,
Choong Won Kim,
Hye Jung Kim,
Won Sup Lee
Affiliations
Young Shin Ko
Department of Pharmacology, College of Medicine, Institute of Health Sciences, Gyeongsang National University, 816 Beongil 15 Jinjudaero, Jinju 52727, Korea
Eun Joo Jung
Departments of Biochemistry, Institute of Health Sciences, Gyeongsang National University College of Medicine, 90 Chilam-dong, Jinju 660-702, Korea
Se-il Go
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
Bae Kwon Jeong
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
Gon Sup Kim
School of Veterinary and Institute of Life Science, Gyeongsang National University, 900 Gajwadong, Jinju 660-701, Korea
Jin-Myung Jung
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
Soon Chan Hong
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
Choong Won Kim
Departments of Biochemistry, Institute of Health Sciences, Gyeongsang National University College of Medicine, 90 Chilam-dong, Jinju 660-702, Korea
Hye Jung Kim
Department of Pharmacology, College of Medicine, Institute of Health Sciences, Gyeongsang National University, 816 Beongil 15 Jinjudaero, Jinju 52727, Korea
Won Sup Lee
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
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.
