Abstract
Abstract Lung cancer is the major cause of cancer-related death in males worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of entire lung cancer and largely metastasizes to bone. Bone consistently maintains the balance between osteoclasts and osteoblasts, but NSCLC metastasized to bone interacts with normal bone cells and abnormally enhances osteoclasts-mediated bone resorption. As a result, enhanced bone resorption results in the release of transforming growth factor-beta (TGF-β) and insulin-like growth factor -1 (IGF-1) which promote cancer progression. Plant-derived compounds have been received attention as therapeutic agents for many human diseases. Artemisinin (ART) which is isolated from chinese medicinal herb, Artemisia annua and its derivative dihydroartemisinin (DHA) have been known as outstanding anti-malarial agents and have also potent anti-cancer activities. ART-glycolipid is ART's derivative that combined ART with the glycolipid daumone in order to enhance anti-cancer activity. We found that cell viability was decreased in A549 cells treated with ART, DHA and ART-glycolipid. ART, DHA and ART-glycolipid decreased the migration of A549 cells treated with or without TGF- β1 and IGF-1 which are highly discovered in bone metastasis of NSCLC. In addition, they inhibited the receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast formation in bone marrow macrophages (BMMs). In particular, ART-glycolipid showed the most potent inhibitory effect. Therefore, we expect that ART, DHA and ART-glycolipid can inhibit metastatic ability of A549 cells and bone resorbing activity of osteoclasts by reducing secretion of matrix metalloproteinases- 9 (MMP-9) and cathepsin K activities in BMM. These results indicate that ART, DHA and ART-glycolipid may serve as useful agents for attenuating NSCLC induced bone destruction. Citation Format: Gwang-Taek Ma, Kwang-Kyun Park, Won-Yoon Chung. The effects of artemisinin, dihydroartemisinin and artemisinin-glycolipid on non-small cell lung cancer induced bone destruction. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2147. doi:10.1158/1538-7445.AM2014-2147
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