Abstract 1870: Polyphenols from Korean artemisia annua L (pKAL) showed anti-cancer effects by multiple mechanisms on HCT116 human colorectal cancer cells

Artemisia annua L., (Gaddongsook in Korean), an annual herb, has been used for a long time in Korean folk medicine for the treatment of infectious or chronic disorder In addition, it possesses anti-inflammatory, and anti-cancer activity. However, the molecular mechanism for anti-cancer properties of Korean Artemisia annua is still unclear. Here, we investigated the anti-cancer effects of we investigated the anti-cancer effects of polyphenols from Korean Artemisia annua (pKAL) on HCT116 human colon cancer cells. pKAL induced cell death associated with the alteration of cell morphology and DNA content. Annexin V and PI staining revealed that late phase apoptosis. pKAL induced ROS generation and the cell death was recovered by NAC. Western blot revealed that pKAL significantly up-regulated the gamma-H2AX, p21, p53, p62 and cleavage of caspases-3 and PARP in HCT116 cells. pKAL induced changes in the expression of p53-dependent targets (p53, p21, Bax, Bak, and Fas). It also induced alteration of the expression of autophagy-related proteins (beclin1, p62, LC3-I, and LC3-II) posttranslational modification of proteins (Lamin A/C, HSP90, GM130) involved in the maintenance of intracellular membrane integrity. Unexpectedly, the effect of pKAL on cell death pKAL was similar in both the P53 wild-type and p53-null HCT116 colon cancer cells, although there was some difference in cell cycle arrest; in P53 wild-type cells, pKAL appeared to induce G1 arrest at lower concentration (50 μg/mL), whereas in p53-null cells, pKAL induced G2/M arrest. The cell death was regulated by JNK and p38 MAPK signaling. The cancer effects of pKAL was similar in p53-null NCI-H1299 cells. We also investigated the protein changes that is related to cell death and cell integrity with anti-body array, which revealed that pKAL induced changes in NF-Kb, PI3K, Ras, TGF-beta signaling too. In conclusion, these findings suggest that pKAL induced anticancer effects by inducing late phase apoptotic cell death at least in part through p38 MAPK and JNK pathways in HCT 1116 human colon cancer cells. It also induced alteration of cell morphology mimic to necrosis in some cells with changes of proteins involved in the maintenance of intracellular membrane integrity. These effects was p53-independent. Citation Format: Won Sup Lee, Anjugam Paramanantham, Eun Joo Jeong, Suchismita Raha, Hye Jung Kim, GonSup Kim, Sung Chul Shin. Polyphenols from Korean artemisia annua L (pKAL) showed anti-cancer effects by multiple mechanisms on HCT116 human colorectal cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1870.