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Small benzothiazole molecule induces apoptosis and prevents metastasis through DNA interaction and c-MYC gene

Felipe Pantoja Mesquita1, Laine Celestino Pinto2, Bruno Moreira Soares2

  • 1Drug 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.

Chemico-Biological Interactions
|August 15, 2018
PubMed

Insights

A novel compound, AFN01, shows significant anticancer potential against gastric cancer cells by inducing cell cycle arrest and apoptosis. It demonstrates selective toxicity towards cancer cells and synergistic effects with doxorubicin, offering a promising avenue for gastric cancer chemotherapy.

Area of Science:

  • Oncology
  • Pharmacology
  • Medicinal Chemistry

Background:

  • Chemo-resistance is a major challenge in gastric cancer treatment.
  • Developing effective and safe anticancer drugs remains a critical need.

Purpose of the Study:

  • To evaluate the anticancer potential of (E)-2-(((2-(benzo[d]thiazo-2-yl)hydrazono)methyl)-4-nitrophenol) (AFN01) against gastric cancer cell lines.
  • To assess the selectivity and synergistic effects of AFN01 in combination with doxorubicin.

Main Methods:

  • In vitro evaluation of AFN01's cytotoxicity against gastric cancer cell lines (ACP-02) and non-malignant cells (MNP-01).
  • Assessment of AFN01's effects on cell cycle progression, cell migration, and apoptosis.
  • Investigation of AFN01's genotoxicity and its synergistic interaction with doxorubicin on cell proliferation and c-MYC gene expression.

Main Results:

  • AFN01 exhibited potent anticancer activity against ACP-02 gastric cancer cells (IC50 = 1.0 μM) and mild activity against MNP-01 cells (IC50 = 3.4 μM).
  • AFN01 induced S phase cell cycle arrest, inhibited cell migration, and triggered apoptosis in a dose-dependent manner.
  • AFN01 demonstrated greater genotoxicity against tumoral cells compared to non-malignant cells and synergized with doxorubicin to suppress proliferation and c-MYC expression.

Conclusions:

  • AFN01 displays significant anticancer properties and selective toxicity against gastric cancer cells.
  • AFN01 holds promise as a lead anticancer agent for gastric cancer treatment, potentially overcoming chemo-resistance.
  • Further pre-clinical and clinical studies are warranted to confirm the safety and efficacy of AFN01.
Keywords:
ApoptosisBenzothiazoleGastric cancerMetastasis profile inhibitionc-MYC gene

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