Disruption of tubulin polymerization and cell proliferation by 1-naphthylarsonic acid.
Arsenical compounds exhibit a differential toxicity to cancer cells. Microtubules are a primary target of a number of anticancer drugs, such as arsenical compounds. The interaction of 1-NAA (1-naphthylarsonic acid) has been investigated on microtubule polymerization under in vitro and cellular conditions. Microtubules were extracted from sheep brain. Transmission electron microscopy was used to show microtubule structure in the presence of 1-NAA. Computational docking method was applied for the discovery of ligand-binding sites on the microtubular proteins. Proliferation of HeLa cells and HF2 (human foreskin fibroblasts) was measured by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay method following their incubation with 1-NAA. Fluorescence microscopic labelling was done with the help of α-tubulin monoclonal antibody and Tunel kit was used to investigate the apoptotic effects of 1-NAA on the HeLa cells. 1-NAA inhibits the tubulin polymerization by the formation of abnormal polymers having high affinity to the inner cell wall.
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, Iran.
Roya
R
Mahinpour
Gholamhossein
G
Riazi
Mohammad A
MA
Shokrgozar
Mohammad N
MN
Sarbolouki
Shahin
S
Ahmadian
Masoumeh
M
Douraghi
Hamid
H
Hadi Alijanvand
Kayhan
K
Azadmanesh
Maryam
M
Heidari
Zahra
Z
Naghdi Gheshlaghi
Ali A
AA
Moosavi-Movahedi
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001152:Arsenicals / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D046529:Microscopy, Electron, Transmission; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008958:Models, Molecular; D058105:Polymerization; D011485:Protein Binding; D012756:Sheep; D013778:Tetrazolium Salts; D013844:Thiazoles; D014020:Tissue Extracts / Q000737:chemistry; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D050257:Tubulin Modulators / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
C574937:1-naphthylarsonic acid; D001152:Arsenicals; D013778:Tetrazolium Salts; D013844:Thiazoles; D014020:Tissue Extracts; D014404:Tubulin; D050257:Tubulin Modulators; C022616:thiazolyl blue