Small benzothiazole molecule induces apoptosis and prevents metastasis through DNA interaction and c-MYC gene supression in diffuse-type gastric adenocarcinoma cell line.

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 (IC50 = 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.

• Authors: Felipe Pantoja Mesquita, Laine Celestino Pinto, Bruno Moreira Soares, Adrhyann Jullyanne de Sousa Portilho, Emerson Lucena da Silva, Ingryd Nayara de Farias Ramos, André Salim Khayat, Caroline Aquino Moreira-Nunes, Mirna Marques Bezerra, Eliza de Lucas Chazin, Thatyana Rocha Alves Vasconcelos, Rommel Mario Rodríguez Burbano, Maria Elisabete Amaral de Moraes, Raquel Carvalho Montenegro
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 294 Pg. 118-127 (Oct 01 2018) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 30107152 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Benzothiazoles
• Proto-Oncogene Proteins c-myc
• DNA
• Caspase 3
• Caspase 7

Topics

• Adenocarcinoma (metabolism, pathology)
• Apoptosis (drug effects)
• Benzothiazoles (chemistry, pharmacology)
• Caspase 3 (metabolism)
• Caspase 7 (metabolism)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• DNA (chemistry, metabolism)
• Down-Regulation (drug effects)
• Humans
• Proto-Oncogene Proteins c-myc (genetics, metabolism)
• Stereoisomerism
• Stomach Neoplasms (metabolism, pathology)