title: Low toxic and high soluble camptothecin derivative 2-47 effectively induces apoptosis of tumor cells in vitro.
abstract: The cytotoxic activity of camptothecin derivatives is so high that these compounds need to be further modified before their successful application as anti-cancer agents clinically. In this study, we reported the synthesis and biological evaluation of a novel camptothecin derivative called compound 2-47. The changes in structure did not reduce its activity to inhibit DNA topoisomerase I. Compound 2-47 induced apoptosis of many tumor cells including leukemia cells K562, Jurkat, HL-60, breast cancer cell BT-549, colon cancer cell HT-29 and liver cancer cell HepG2 with a half maximal inhibitory concentration (IC50) of 2- to 3-fold lower than HCPT as a control. In particular, 2-47 inhibited the proliferation of Jurkat cells with an IC50 of as low as 40 nM. By making use of Jurkat cell as a model, following treatment of Jurkat cells, compound 2-47 activated caspase-3 and PARP, resulting in a decreased Bcl-2/Bax ratio. These data showed that compound 2-47 induces Jurkat cell death through the mitochondrial apoptotic pathway. In addition, compound 2-47 showed a decreased cytotoxic activity against normal cells and an improved solubility in low-polar solvent. For example, compound 2-47 solutes in CHCl3 130-fold higher than HCPT. Taken together, our data demonstrated that camptothecin derivative 2-47 notably inhibits the tumor cell proliferation through mitochondrial-mediated apoptosis in vitro.
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Tianjin Key Laboratory of Industrial Microbiology, Sino-French Joint Laboratory of Food Nutrition, Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin 300457, PR China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Tianjin Key Laboratory of Industrial Microbiology, Sino-French Joint Laboratory of Food Nutrition, Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin 300457, PR China.
authors.forename: Hong-Ye
authors.initials: HY
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Tianjin Key Laboratory of Industrial Microbiology, Sino-French Joint Laboratory of Food Nutrition, Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin 300457, PR China.
authors.forename: Du
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Tianjin Key Laboratory of Industrial Microbiology, Sino-French Joint Laboratory of Food Nutrition, Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin 300457, PR China.
authors.forename: Lu-Yao
authors.initials: LY
authors.lastname: Wang
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Tianjin Key Laboratory of Industrial Microbiology, Sino-French Joint Laboratory of Food Nutrition, Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin 300457, PR China.
authors.forename: Cen
authors.initials: C
authors.lastname: Xiang
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Tianjin Key Laboratory of Industrial Microbiology, Sino-French Joint Laboratory of Food Nutrition, Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin 300457, PR China.
authors.forename: Shao-Peng
authors.initials: SP
authors.lastname: Wen
authors.affiliation: Key Laboratory of Food Nutrition and Safety (Tianjin University of Science & Technology), Ministry of Education, Tianjin, 300457, PR China; Obesita & Algaegen LLC, College Station, TX 77845, USA.
authors.forename: Zhen-Chuan
authors.initials: ZC
authors.lastname: Fan
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Institut Parisien de Chimie Moléculaire UMR CNRS 8232, 4 place Jussieu, 75005, Paris, France.
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Tianjin Key Laboratory of Industrial Microbiology, Sino-French Joint Laboratory of Food Nutrition, Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin 300457, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Guo
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Tianjin Key Laboratory of Industrial Microbiology, Sino-French Joint Laboratory of Food Nutrition, Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin 300457, PR China. Electronic address: tyo201485@tust.edu.cn.
authors.forename: Yu-Ou
authors.initials: YO
authors.lastname: Teng
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Tianjin Key Laboratory of Industrial Microbiology, Sino-French Joint Laboratory of Food Nutrition, Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin 300457, PR China. Electronic address: yupeng@tust.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002166:Camptothecin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000633:toxicity; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology*; D012995:Solubility; D016896:Treatment Outcome
chemical_list: D002166:Camptothecin
keywords: Apoptosis; Camptothecin derivatives; DNA topoisomerase I