title: Morphological Evaluation of Nonlabeled Cells to Detect Stimulation of Nerve Growth Factor Expression by Lyconadin B.
abstract: The success of drug development is greatly influenced by the efficiency of drug screening methods. Recently, phenotype-based screens have raised expectations, based on their proven record of identifying first-in-class drugs at a higher rate. Although fluorescence images are the data most commonly used in phenotype-based cell-based assays, nonstained cellular images have the potential to provide new descriptive information about cellular responses. In this study, we applied morphology-based evaluation of nonlabeled microscopic images to a phenotype-based assay. As a study case, we attempted to increase the efficiency of a cell-based assay for chemical compounds that induce production of nerve growth factor (NGF), using lyconadin B as a model compound. Because the total synthesis of lyconadin B was accomplished very recently, there is no well-established cell-based assay scheme for further drug screening. The conventional cell-based assay for evaluating NGF induction requires two types of cells and a total of 5 days of cell culture. The complexity and length of this assay increase both the risk of screening errors and the cost of screening. Our findings show that analysis of cellular morphology enables evaluation of NGF induction by lyconadin B within only 9 h.
authors.affiliation: Division of Bioscience, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Kawai
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Nagoya University, Nagoya, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Division of Bioscience, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Okada
authors.affiliation: Division of Bioscience, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Kanie
authors.affiliation: Division of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yokoshima
authors.affiliation: Division of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Fukuyama
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Nagoya University, Nagoya, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Honda
authors.affiliation: Division of Bioscience, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, Japan kato-r@ps.nagoya-u.ac.jp.ac.jp.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kato
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020932:Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D011083:Polycyclic Compounds / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D011083:Polycyclic Compounds; C514204:lyconadin B; D020932:Nerve Growth Factor
keywords: cellular morphology; image-based cellular evaluation; nerve growth factor; phenotype-based screening