development of resistance towards artesunate in mda-mb-231 human breast cancer cells电阻对青蒿琥酯的发展在人类乳腺癌mda - mb - 231细胞.pdfVIP

Development of Resistance towards Artesunate in MDA- MB-231 Human Breast Cancer Cells 1,2 3 1 1 2 Beatrice Bachmeier , Iduna Fichtner , Peter H. Killian , Emanuel Kronski , Ulrich Pfeffer , Thomas Efferth4* 1 Department of Clinical Chemistry and Clinical Biochemistry, Ludwig-Maximilians-University, Munich, Germany, 2 Functional Genomics, Advanced Biotechnology Center, ¨ Genoa, Italy, 3 Department of Experimental Pharmacology, Max Delbruck-Center for Molecular Medicine, Berlin, Germany, 4 Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany Abstract Breast cancer is the most common cancer and the second leading cause of cancer death in industrialized countries. Systemic treatment of breast cancer is effective at the beginning of therapy. However, after a variable period of time, progression occurs due to therapy resistance. Artesunate, clinically used as anti-malarial agent, has recently revealed remarkable anti-tumor activity offering a role as novel candidate for cancer chemotherapy. We analyzed the anti-tumor effects of artesunate in metastasizing breast carcinoma in vitro and in vivo. Unlike as expected, artesunate induced resistance in highly metastatic human breast cancer cells MDA-MB-231. Likewise acquired resistance led to abolishment of apoptosis and cytotoxicity in pre-treated MDA-MB-231 cells. In contrast, artesunate was more cytotoxic towards the less tumorigenic MDA-MB-468 cells without showing resistance. Unraveling the underlying molecular mechanisms, we found that resistance was induc