B1, a novel naphthalimide-based DNA intercalator, induces cell cycle arrest and apoptosis in HeLa cells via p53 activation.
In the course of screening for novel anticancer compounds, B1 (N-(2-(Dimethylamino)ethyl)-2-aminothiazonaphthalimide), a novel naphthalimide-based DNA intercalator, was generated as a new anticancer candidate. For the first time, our investigation demonstrates that B1 inhibited the growth of HeLa cells by the induction of cell cycle arrest and apoptosis. Analysis of flow cytometry and western blots of HeLa cells treated with B1 revealed an appreciable cell cycle arrest and apoptotic induction in dose and time-dependent manner via the p53-dependent pathway. Furthermore, the release of cytochrome c from mitochondria was detected using confocal microscopy in HeLa cells treated with B1. Accordingly, these data demonstrate that the anticancer activity of B1 is associated with the activation of p53 and the release of cytochrome c, which suggest that B1 might have therapeutic potential against cervix carcinoma as an effective lead compound.
Liang
Xin
X
State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of Chemical Biology, School of pharmacy, East China University of Science and Technology, Shanghai, 200237, People's Republic of China.
Wu
Aibin
A
Xu
Yufang
Y
Xu
Ke
K
Liu
Jianwen
J
Qian
Xuhong
X
D000225:Adenine; D017209:Apoptosis / Q000187:drug effects*; D052160:Benzothiazoles / Q000737:chemistry / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004273:DNA, Neoplasm / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005453:Fluorescence; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007364:Intercalating Agents / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D053644:Naphthalimides / Q000737:chemistry / Q000494:pharmacology*; D009336:Necrosis; D063065:Organophosphonates; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D013194:Staining and Labeling; D013997:Time Factors; D014410:Tumor Stem Cell Assay; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D052160:Benzothiazoles; D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D007364:Intercalating Agents; C556398:N-(2-(dimethylamino)ethyl)-2-aminothiazonaphthalimide; D053644:Naphthalimides; D063065:Organophosphonates; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; C037020:amonafide; D045304:Cytochromes c; D020169:Caspases; D000225:Adenine