title: Fluoride-containing podophyllum derivatives exhibit antitumor activities through enhancing mitochondrial apoptosis pathway by increasing the expression of caspase-9 in HeLa cells.
abstract: This work aims to provide sampling of halogen-containing aniline podophyllum derivatives and their mode of action with an in-depth comparison among fluorine, chloride and bromide for clarifying the important role and impact of fluorine substitution on enhancing antitumor activity, with an emphasis on the development of drug rational design for antitumor drug. The tumor cytotoxicity of fluoride-containing aniline podophyllum derivatives were in general improved by 10-100 times than those of the chloride and bromide-containing aniline podophyllum derivatives since fluoride could not only strongly solvated in protic solvents but also forms tight ion pairs in most aprotic solvents. When compared with chloride and bromide, the higher electronegativity fluoride substituted derivatives significantly enhanced mitochondrial apoptosis pathway by remarkably increasing the expression of caspase-9 in HeLa cells. The current findings would stimulate an enormous amount of research directed toward exploiting novel leading compounds based on podophyllum derivatives, especially for the fluoride-substituted structures with promising antitumor activity.
authors.affiliation: Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Key Laboratory of Industrial Microbiology, Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei University of Technology, Wuhan 430068 China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Key Laboratory of Industrial Microbiology, Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei University of Technology, Wuhan 430068 China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Key Laboratory of Industrial Microbiology, Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei University of Technology, Wuhan 430068 China.
authors.forename: Ya-Xuan
authors.initials: YX
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Key Laboratory of Industrial Microbiology, Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei University of Technology, Wuhan 430068 China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Key Laboratory of Industrial Microbiology, Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei University of Technology, Wuhan 430068 China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041 China.
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041 China.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Liang
authors.affiliation: Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Key Laboratory of Industrial Microbiology, Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei University of Technology, Wuhan 430068 China.
authors.forename: Ya-Jie
authors.initials: YJ
authors.lastname: Tang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D055162:Biocatalysis / Q000187:drug effects; D015153:Blotting, Western; D053453:Caspase 9 / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005459:Fluorides / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D011035:Podophyllum / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D053453:Caspase 9; D004250:DNA Topoisomerases, Type II; D005459:Fluorides; D003078:Colchicine