Antitumor effects of Auraptene in 4T1 tumor-bearing Balb/c mice

Horm Mol Biol Clin Investig. 2021 Mar 8;42(3):245-252. doi: 10.1515/hmbci-2020-0090.

Abstract

Objectives: Breast cancer is a common malignant tumor in women with limited treatment options and multiple side effects. Today, the anti-cancer properties of natural compounds have attracted widespread attention from researchers worldwide.

Methods: In this study, we treated 4T1 tumor-bearing Balb/c mice with intraperitoneal injection of Auraptene, paraffin oil, and saline as two control groups. Body weight and tumor volume were measured before and after treatment. Hematoxylin and eosin (H & E) staining and immunohistochemistry of Ki-67 were used as markers of proliferation. In addition, ELISA assays were performed to assess serum IFN-γ and IL-4 levels.

Results: There was no significant change in body weight in all animal groups before and after treatment. 10 days after the last treatment, Auraptene showed its anti-cancer effect, which was confirmed by the smaller tumor volume and H & E staining. In addition, Ki-67 expression levels were significantly reduced in tumor samples from the Auraptene-treated group compared to the paraffin oil and saline-treated groups. In addition, in tumor-bearing and normal mice receiving Auraptene treatment, IL-4 serum production levels were reduced, while serum levels of IFN-γ were significantly up-regulated in tumor-bearing mice after Auraptene treatment.

Conclusions: In the case of inhibition of tumor volume and Ki-67 proliferation markers, Auraptene can effectively inhibit tumor growth in breast cancer animal models. In addition, it might increases Th1 and CD8 + T cell responses after reducing IL-4 serum levels and IFN-γ upregulation, respectively. However, further research is needed to clarify its mechanism of action.

Keywords: Auraptene; angiogenesis; anti-angiogenesis; breast cancer; immunostimulatory activity; natural compounds.

MeSH terms

  • Allografts
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Biological Products / chemistry
  • Biological Products / pharmacology*
  • Biomarkers, Tumor
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / etiology
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Coumarins / chemistry
  • Coumarins / pharmacology*
  • Cytokines / blood
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Immunohistochemistry
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Tumor Burden / drug effects

Substances

  • Antineoplastic Agents
  • Biological Products
  • Biomarkers, Tumor
  • Coumarins
  • Cytokines
  • aurapten