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2014 MRC성과발표회 Abstract Information [ ] 심포지엄 구연 발표 [ O ] 기초의과학 학문후속세대 발표 Category (연제와 관련있는 분야에 모두 표시해 주십시오) [ ] Aging and age-related diseases [ O ] Alternative medicine [ ] Anatomical methodology [ O ] Anticancer strategies [ ] Bioengineering and technology [ ] Biology of development [ ] Biomarkers for personalized medicine [ ] Biomedical informatics [ ] Cancer biology (oncological sciences) [ ] Cellular injuries, death, apoptosis, autophagy [ ] Clinical pharmacology [ ] Craniofacial diseases [ ] Developmental Biology and Cell Differentiation [ ] DNA Replication, DNA Damage and Cell Cycle [ ] Drug: mechanism of action & toxicity [ ] Endocrinology and metabolism [ ] Enzyme: mechanism of action and regulation [ ] Gene expression [ ] Gene-, Cell-, & Immunotherapy [ ] Genetics and Epigenetics [ ] Gross anatomy [ ] Herb medicine and phytochemicals [ ] Histology of organs [ ] Immunology [ ] Inflammation and tissue injury [ ] Infectious diseases: bacteriology, virology and mycology [ ] Ion, ion channel & excitability [ ] Membrane transport & secretion [ ] Metabolic diseases [ ] Molecular and Cellular Aspects of Behaviour [ ] Neuroscience and Neurobiology [ O ] Novel Targets for Drug Development and Screening Candidates [ ] Omics and Systems Biology [ ] Orofacial Diseases [ ] Protein Biochemistry: Structure, Function, and Modification [ ] Parasitology and parasitic diseases [ ] Pharmacogenetics [ ] Preventive medicine [ ] RNA Biology and Application [ ] Signal transduction [ ] Stem cells and regeneration [ ] Therapeutic approaches of Korean Medicine [ ] Vascular Biology and Medicine [ ] 기타 ( ) < Abstract Sample > Alantolactone selectively suppresses STAT3 activation and exhibits potent anticancer activity in MDA-MB-231 cells Jaemoo Chun, Kwang Ho Song, Yeong Shik Kim Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea The important goal of cancer drug discovery is to develop therapeutic agents that are effective, safe, and affordable. In the present study, we demonstrated that alantolactone, which is a sesquiterpene lactone, has potential activity against triple-negative breast cancer MDA-MB-231 cells by suppressing the signal transducer and activator of transcription 3 (STAT3) signaling pathway. Alantolactone effectively suppressed both constitutive and inducible STAT3 activation at tyrosine 705. Alantolactone decreased STAT3 translocation to the nucleus, its DNA-binding, and STAT3 target gene expression. Alantolactone is shown to significantly inhibit STAT3 activation with marginal effect on MAPKs and on NF-κB transcription but is not mediated through inhibiting STAT3 upstream kinases. Although SHP1, SHP-2, and PTEN were not affected by alantolactone, the treatment with pervanadate, which is a protein tyrosine phosphatase (PTP) inhibitor, reversed the alantolactone-induced STAT3 inactivation, indicating an important role of PTP in the action of alantolactone. Finally, alantolactone treatment resulted in the inhibition of migration, invasion, adhesion, and colony formation. Remarkably, the in vivo administration of alantolactone inhibited the growth of human breast xenograft tumors. These results provide preclinical evidence for further studies of the development of alantolactone as a STAT3 inhibitor and as a potential candidate against breast cancer. References [1] [2] [3] Keywords STAT3, Alantolactone, Sesquiterpene lactone, Triple-negative breast cancer (TNBC) 2014 MRC 성과발표회 Name : Jaemoo Chun Affiliation : Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea Position : Post-Doc. E-mail : [email protected] Field of Expertise : Inflammation and cancer Transcription factors Chemopreventive agents Education : Ph.D. (2009-2014) - Seoul National University, College of Pharmacy, Natural Products Research Institute BS (2005-2009) - Wonkwang University, College of Pharmacy, Department of Oriental Pharmacy Professional Experience : (less than 5 experiences) Post-Doc. (2014-Present) - Seoul National University, College of Pharmacy, Natural Products Research Institute Selected Publications : (less than 5 papers) [1] Chun J, Kang M, Kim YS. A triterpenoid saponin from Adenophora triphylla var. japonica suppresses the growth of human gastric cancer cells via regulation of apoptosis and autophagy. Tumour Biol. Epub ahead of print, 2014 Aug. [2] Chun J, Han L, Xu MY, Wang B, Cheng MS, Kim YS. Induction of apoptosis by a newly synthesized diosgenyl saponin through suppression of estrogen receptor-α in MCF-7 human breast cancer cells. Arch Pharm Res. 37(11):1477-86, 2014 Nov. [3] Chun J, Kim YS. Platycodin D inhibits migration, invasion, and growth of MDA-MB-231 human breast cancer cells via suppression of EGFR-mediated Akt and MAPK pathways. Chem Biol Int. 205(3):212-221, 2013 Oct. [4] Chun J, Ha IJ, Kim YS. Anti-proliferative and apoptotic activities of triterpenoid saponins from the roots of Platycodon grandiflorum and their structure-activity relationships. Planta Med. 79(8):639-645, 2013 May. [5] Chun J, Joo EJ, Kang M, Kim YS. Platycodin D induces anoikis and caspase-mediated apoptosis via p38 MAPK in AGS human gastric cancer cells. J Cell Biochem. 114(2), 456470, 2013 Feb.