1. Small benzothiazole molecule induces apoptosis and prevents metastasis through DNA interaction and c-MYC gene supression in diffuse-type gastric adenocarcinoma cell line.
- Author
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Mesquita FP, Pinto LC, Soares BM, de Sousa Portilho AJ, da Silva EL, de Farias Ramos IN, Khayat AS, Moreira-Nunes CA, Bezerra MM, de Lucas Chazin E, Vasconcelos TRA, Burbano RMR, de Moraes MEA, and Montenegro RC
- Subjects
- Adenocarcinoma metabolism, Adenocarcinoma pathology, Benzothiazoles chemistry, Caspase 3 metabolism, Caspase 7 metabolism, Cell Cycle Checkpoints drug effects, Cell Line, Tumor, Cell Movement drug effects, Cell Proliferation drug effects, DNA chemistry, Down-Regulation drug effects, Humans, Proto-Oncogene Proteins c-myc genetics, Stereoisomerism, Stomach Neoplasms metabolism, Stomach Neoplasms pathology, Apoptosis drug effects, Benzothiazoles pharmacology, DNA metabolism, Proto-Oncogene Proteins c-myc metabolism
- Abstract
Chemo-resistance has been reported as a relevant barrier for the efficiency of gastric cancer treatment. Therefore, the development of effective and safe drugs for cancer chemotherapy is still a challenge. The purpose of this study was to evaluate the anticancer potential of (E)-2-(((2-(benzo[d]thiazo-2-yl)hydrazono)methyl)-4-nitrophenol) (AFN01) against gastric cancer cell lines. Our results showed promising anticancer activity against gastric cancer cells ACP-02 (IC
50 = 1.0 μM) and mild activity against other cell lines including non-malignant gastric cell MNP-01 (IC50 = 3.4 μM). This compound significantly induced S phase cell cycle arrest, prevented cell migration and triggered apoptosis in a concentration-dependent manner. Moreover, AFN01 was significantly more genotoxic against tumoral cell ACP-02, when compared to non-malignant cells, such as MNP-01 and healthy peripheral mononuclear blood cells. AFN01 also synergistically interacts with doxorubicin suppressing cell proliferation and c-MYC gene expression in gastric cancer cell line model, with remarkable c-MYC overexpression. Although further pre-clinical and clinical studies are required to explore its safety and efficiency, AFN01 may represent a promising lead anticancer agent for the treatment of gastric cancer., (Copyright © 2018 Elsevier B.V. All rights reserved.)- Published
- 2018
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