Anticancer potential of benzothiazolic derivative (E)-2-((2-(benzo[d]thiazol-2-yl)hydrazono)methyl)-4-nitrophenol against melanoma cells

被引:12
|
作者
Vasconcelos, Zanair Soares [1 ]
Lima Ralph, Ana Carolina [1 ]
Calcagno, Danielle Queiroz [2 ]
Barbosa, Gleyce dos Santos [1 ]
Pedrosa, Tatiana do Nascimento [1 ]
Antony, Lucas Pio [1 ]
Cardoso Smith, Marllia de Arruda [3 ]
Chazin, Eliza de Lucas [4 ]
Alves Vasconcelos, Thatyana Rocha [4 ]
Montenegro, Raquel Carvalho [5 ]
de Vasconcellos, Marne Carvalho [1 ]
机构
[1] Fed Univ Amazon, Fac Pharmaceut Sci, Amazon, Brazil
[2] Fed Univ Para, Ctr Oncol Res, Belem, Para, Brazil
[3] Univ Fed Sao Paulo, Paulista Sch Med, Dept Morphol & Genet, Sao Paulo, Brazil
[4] Fluminense Fed Univ, Chem Inst, Rio De Janeiro, Brazil
[5] Univ Fed Ceara, Drug Res & Dev Ctr, Fac Med, Fortaleza, Ceara, Brazil
关键词
AFN01; B-RAF; Cutaneous melanoma; Cytotoxicity; LI-FRAUMENI-SYNDROME; IN-VITRO; (E)-2-BENZOTHIAZOLE HYDRAZONES; CANCER METASTASIS; COMET ASSAY; DNA-DAMAGE; P53; ANTITUMOR; DESIGN; INHIBITOR;
D O I
10.1016/j.tiv.2018.03.001
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Malignant melanoma is an important type of cancer worldwide due to its aggressiveness and poor survival rate. Significant efforts to understand the biology of melanoma and approaches to treat the advanced disease are focused on targeted gene inhibitors. Frequently mutated genes, such as NRAS, B-RAF and TP53, significantly exceed the frequency of mutations of other genes, emphasizing their importance for future targeted therapies. Considering the antitumor activity of benzothiazolic derivatives, this study aimed to demonstrate the action of benzothiazolic (E)-2((2-(benzo[d]thiazol-2-yl)hydrazono)methyl)-4-nitrophenol (AFN01) against three established human melanoma cell lines that recapitulate the molecular landscape of the disease in terms of its genetic alterations and mutations, such as the TP53, NRAS and B-RAF genes. The results presented here indicate that AFN01, as a significant cytostatic and cytotoxic drug due to its induction of DNA fragmentation, causes single and double DNA strand breaks, consequently inhibiting cell proliferation, migration and invasion by promoting apoptosis. Our data suggest that AFN01 might be considered as a future therapeutic option for managing melanoma.
引用
收藏
页码:225 / 235
页数:11
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