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

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.

Doxorubicin-Resistant TNBC Cells Exhibit Rapid Growth with Cancer Stem Cell-like Properties and EMT Phenotype, Which Can Be Transferred to Parental Cells through Autocrine Signaling

“…This finding is more appealing to us and is consistent with our own findings. In addition, we previously demonstrated that radiation-resistant MDA-MB 231 cells were also highly proliferative while they exhibited an enrichment of the EMT features with CSC properties [42]. All this supports our findings.…”

Knockdown of CD44 inhibits proliferation, migration and invasion of osteosarcoma cells accompanied by downregulation of cathepsin S

“…Both matrix metalloproteinases and CD44 are critical for tumour invasion. MMP-9 has been shown to be associated with CD44 on breast cancer cells [33] and human melanoma cells [34]. Mt1-MMP can cleave CD44 and promote cell migration in pancreatic tumour cell lines [35].…”

Artemisia santolinifolia-Mediated Chemosensitization via Activation of Distinct Cell Death Modes and Suppression of STAT3/Survivin-Signaling Pathways in NSCLC

“…The chemical constituents of A. santolinifolia , such as terpenoids, polyacetylenes, coumarins, glycosides, sterols, and flavonoids, were documented in several studies [ 16 , 17 , 18 ]. Furthermore, previous studies have reported in vitro and in vivo cytotoxic and antitumor effects of various Artemisia species and the related molecular pathways, such as activation of caspase, modulation of Bax/Bcl-2 ratio and generation of ROS level, subsequent cell cycle arrest at S, G2/M phase, as well as inhibition of specific target molecules—notch 1, β-catenin, and MMP9 [ 19 , 20 , 21 ]. However, the anticancer activity of A. santolinifolia combined with conventional chemotherapeutic docetaxel (DTX) has not yet been investigated.…”