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Abstract
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.

Author information

Ko YS1, Jung EJ2, Go SI3, Jeong BK4, Kim GS5, Jung JM6, Hong SC7, Kim CW2, Kim HJ1, Lee WS3.
1
Department of Pharmacology, College of Medicine, Institute of Health Sciences, Gyeongsang National University, 816 Beongil 15 Jinjudaero, Jinju 52727, Korea.
2
Departments of Biochemistry, Institute of Health Sciences, Gyeongsang National University College of Medicine, 90 Chilam-dong, Jinju 660-702, Korea.
3
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.
4
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.
5
School of Veterinary and Institute of Life Science, Gyeongsang National University, 900 Gajwadong, Jinju 660-701, Korea.
6
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.
7
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.