title: Screening of anti-cancer agent using zebrafish: comparison with the MTT assay.
abstract: The MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide) assay is a classical method for screening cytotoxic anti-cancer agents. Candidate drugs from the MTT assay need in vivo models to test their efficiency and to assess the absorption, distribution, metabolism, excretion, and toxicity of the drugs. An in vivo screening model could increase the rate of development of anti-cancer drugs. Here, we used zebrafish to screen a library of 502 natural compounds and compared the results with those from an MTT assay of the MCF7 breast cancer cell line. We identified 59 toxic compounds in the zebrafish screen, 21 of which were also identified by the MTT assay, and 28 of which were already known for their anti-cancer and apoptosis-inducing effects. These compounds induced apoptosis and activated the p53 pathway in zebrafish within 3h treatment. Our results indicate that zebrafish is a simple, reliable and highly efficient in vivo tool for cancer drug screening, and could complement the MTT assay.
authors.affiliation: Drug Discovery Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Yigen
authors.initials: Y
authors.lastname: Li
authors.forename: Wenjin
authors.initials: W
authors.lastname: Huang
authors.forename: Shenyuan
authors.initials: S
authors.lastname: Huang
authors.forename: Jiulin
authors.initials: J
authors.lastname: Du
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology; D045744:Cell Line, Tumor; D004396:Coloring Agents / Q000737:chemistry; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004642:Emodin / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D017705:Lignans / Q000494:pharmacology; D009285:Naphthoquinones / Q000494:pharmacology; D012402:Rotenone / Q000494:pharmacology; D013778:Tetrazolium Salts / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D015027:Zebrafish; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D002166:Camptothecin; D004396:Coloring Agents; D004121:Dimethyl Sulfoxide; D004642:Emodin; D017705:Lignans; D009285:Naphthoquinones; D012402:Rotenone; D013778:Tetrazolium Salts; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols; C014638:beta-lapachone; C022616:thiazolyl blue