Abstract 4103: Polyphenols from Artemisia annua L (pKAL) exhibit anticancer effects on radio-resistant MDA-MB-231 cells by suppressing stemness phenotype and EMT process

Artemisia annua L., (Gaddongsook in Korean) has been used as Korean folk medicine for anti-inflammatory, and anticancer activities. However, the molecular mechanisms for anti-cancer activities of Artemisia annua L. still need elucidating. Here, we determine whether pKAL exhibit the anti-cancer effects on RT-R breast cancer cells, and the molecular characteristics for the radio-resistant (RT-R) breast cancer. In addition, we further explore the molecular mechanisms for anticancer effects of pKAL on stemness and epithelial-mesenchymal transition (EMT). MTT and colony forming assay revealed that pKAL inhibited cell proliferation on both RT-R-MDA-MB-231 cells and MDA-MB-231 cells in a dose- and time-dependent manner. GO enrichment analysis of differentially expressed proteins between RT-R-MDA-MB-231 cells and MDA-MB-231 cells with the use of KEGG pathway analysis and PANTHER functional analysis revealed that MAPK signaling pathway might be used as a survival mechanism for the RT R-MDA-MB-231 cells to attain the resistance. The detailed western blot analysis for anti-cancer effects of pKAL revealed that it inhibited the expression of CD44 and Oct 3/4 (stem cell markers), and β-catenin and MMP-9 (EMT markers) of RT-R-MDA-MB-231 cells. In addition, pKAL inhibited STAT 3 activity that is upregulated in RT-R-MDA-MB-231 cells compared to in parental MDA-MB-231 cells. JNK and JAK2 inhibitors also inhibited STAT3 activity on both RT-R-MDA-MB-231 cells and MDA-MB-231 cells. However, JNK or JAK2 inhibitor could not suppress nor augment the anti-cancer effects of pKAL on CD44, and Oct 3/4 expression while JAK2 inhibitor could inhibit the expression of β-catenin, and MMP-9 expression. These findings suggest that pKAL-induced anticancer effects are not closely associated with JNK and JAK2/STAT3 signaling. In conclusion, this study suggested pKAL exhibit anticancer effects on radio-resistant MDA-MB-231 cells by suppressing stemness phenotype and EMT. Citation Format: Won Sup Lee, Yougn Shin Ko, Anjugam paramanantham, GonSup Kim, Sung Chul Shin, Hye Jung Kim. Polyphenols from Artemisia annuaL (pKAL) exhibit anticancer effects on radio-resistant MDA-MB-231 cells by suppressing stemness phenotype and EMT process [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4103.