title: Discovery of 3-phenylquinolinylchalcone derivatives as potent and selective anticancer agents against breast cancers.
abstract: A number of 3-phenylquinolinylchalcone derivatives were synthesized and evaluated in vitro for their antiproliferative activities against three breast cancer cell lines (MCF-7, MDA-MB-231, and SKBR-3), and a non-cancer normal epithelial cell line (H184B5F5/M10). Among them, (E)-3-[3-(4-methoxyphenyl)quinolin-2-yl]-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (7) was active against the growth of MCF-7, MDA-MB-231, and SKBR-3 with IC50 values of 1.05, 0.75, and 0.78 μM respectively without significant cytotoxicity to the normal H184B5F5/M10 cell line and therefore, was selected as a new lead for further mechanism studies. Results indicated that compound 7 inhibited the polymerization of tubulins, induced G2/M cell cycle arrest via modulation of the cyclin B1, cdk1 and CDC25. Compound 7 ultimately induced cell apoptosis by the increase of apoptotic protein Bax and the decrease of anti-apoptotic protein Bcl-2. In addition, PARP was cleaved while caspase-3 and -8 activities were induced after the treatment of compound 7 for 24 h in a concentration-dependent manner. Thus, compound 7 induces cell cycle arrest at G2/M phase via cleavage of PARP, induces caspase-3 and -8 activities and consequently to cause the cell death. Further study on the structure optimization of 7 is ongoing.
authors.affiliation: School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung City 807, Taiwan; Research Center for Natural Products & Drug Development, Kaohsiung Medical University, Kaohsiung City 807, Taiwan.
authors.forename: Chih-Hua
authors.initials: CH
authors.lastname: Tseng
authors.affiliation: Research Center for Natural Products & Drug Development, Kaohsiung Medical University, Kaohsiung City 807, Taiwan; Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung City 807, Taiwan.
authors.forename: Cherng-Chyi
authors.initials: CC
authors.lastname: Tzeng
authors.affiliation: Research Center for Natural Products & Drug Development, Kaohsiung Medical University, Kaohsiung City 807, Taiwan; Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung City 807, Taiwan.
authors.forename: Chih-Yao
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung City 807, Taiwan.
authors.forename: Chih-Mei
authors.initials: CM
authors.lastname: Cheng
authors.affiliation: Department of Life Science, National University of Kaohsiung, 700 Kaohsiung University Rd, Kaohsiung, Taiwan. Electronic address: cnyang@nuk.edu.tw.
authors.forename: Chia-Ning
authors.initials: CN
authors.lastname: Yang
authors.affiliation: Research Center for Natural Products & Drug Development, Kaohsiung Medical University, Kaohsiung City 807, Taiwan; Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung City 807, Taiwan. Electronic address: yeloch@kmu.edu.tw.
authors.forename: Yeh-Long
authors.initials: YL
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016203:CDC2 Protein Kinase / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002599:Chalcone / Q000737:chemistry*; D056744:Cyclin B1 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D055808:Drug Discovery; D005260:Female; D005455:Fluorescent Antibody Technique; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D008958:Models, Molecular; D015394:Molecular Structure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011804:Quinolines / Q000737:chemistry*; D015363:Quinolones / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000378:metabolism
chemical_list: C000602531:3-(3-(4-methoxyphenyl)acryloyl)-4-phenyl-1H-quinolin-2-one; D000970:Antineoplastic Agents; D056744:Cyclin B1; D019253:Proto-Oncogene Proteins c-bcl-2; D011804:Quinolines; D015363:Quinolones; D051028:bcl-2-Associated X Protein; D002599:Chalcone; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D020687:cdc25 Phosphatases
keywords: 3-Phenylquinolinylchalcone derivatives; Anticancer agents; Apoptosis; Breast cancers; Cell cycle