Drug Research and Development Center (NPDM), Federal University of Ceará - Rua Cel, Nunes de Melo, n.1000 - Rodolfo Teófilo, Fortaleza, CE, Brazil; Biological Science Institute, Federal University of Pará - Rua Augusto Correa, n.01 - Guamá, Belem, Pará, Brazil.
Biological Science Institute, Federal University of Pará - Rua Augusto Correa, n.01 - Guamá, Belem, Pará, Brazil.
Chem Biol Interact. 2018 Oct 1;294:118-127. doi: 10.1016/j.cbi.2018.08.006. Epub 2018 Aug 11.
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 = 1.0 μM) and mild activity against other cell lines including non-malignant gastric cell MNP-01 (IC = 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.
化疗耐药性已被报道为胃癌治疗效率的一个相关障碍。因此，开发有效和安全的癌症化疗药物仍然是一个挑战。本研究的目的是评估（E）-2-(((2-(苯并[d]噻唑-2-基)腙基)甲基)-4-硝基苯酚)（AFN01）对胃癌细胞系的抗癌潜力。我们的结果显示，该化合物对胃癌细胞 ACP-02 具有有前景的抗癌活性（IC=1.0 μM），对其他细胞系包括非恶性胃细胞 MNP-01（IC=3.4 μM）具有轻度活性。该化合物以浓度依赖的方式显著诱导 S 期细胞周期停滞，阻止细胞迁移并触发细胞凋亡。此外，与非恶性细胞（如 MNP-01 和健康外周血单核细胞）相比，AFN01 对肿瘤细胞 ACP-02 的遗传毒性明显更大。AFN01 还与阿霉素协同作用，抑制胃癌细胞模型中的细胞增殖和 c-MYC 基因表达，对 c-MYC 过表达具有显著抑制作用。尽管需要进一步的临床前和临床研究来探索其安全性和有效性，但 AFN01 可能代表一种有前途的抗癌先导药物，用于治疗胃癌。
