Gemini curcumin inhibits 4T1 cancer cell proliferation and modulates the expression of apoptotic and metastatic genes in Balb/c mice model

Pathol Res Pract. 2023 Mar:243:154344. doi: 10.1016/j.prp.2023.154344. Epub 2023 Jan 24.

Abstract

Background: Despite the attractive anti-cancer effects, poor solubility and low bioavailability have restricted the clinical application of Curcumin. Recent findings show that Gemini nano-curcumin (Gemini-Cur) significantly improves the cellular uptake of Curcumin and its anti-cancer effect in tumor cells. Here, we aimed to assess the suppressive effect of Gemini-Cur on 4T1 breast cancer cells in vitro and, subsequently, in BALB/c mouse models.

Materials and methods: Fluorescence microscopy was employed to visualize cellular uptake and morphological changes of 4T1 cells during treatment with Gemini-Cur and void curcumin. MTT and annexin V/FITC assays were performed to study the toxic effect of Gemini-Cur on mouse cancer cells. For in vivo studies, BALB/c tumor-bearing mice were used to evaluate the inhibitory effect of Gemini-Cur in comparison with mice receiving free Curcumin and nanoparticles.

Results: Our data showed that Gemini-Cur enters the cells and inhibits proliferation in a time- and dose-dependent manner. Annexin V/FITC confirmed apoptotic effect on 4T1 cells. In vivo studies also illustrated that tumor growth is suppressed in Gemini-Cur treated mice rather than controls. Expression studies demonstrated the modulation of apoptotic and metastatic genes, including Bax, Bcl-2, MMP-9, VEGF, and COX-2 in treated mice.

Conclusion: In conclusion, these data demonstrate the promising anti-cancer properties of Gemini-Cur on mice models. However, further studies at molecular and cellular levels are required to conclude this therapeutic advantage.

Keywords: 4T1; BALB/c; Breast cancer; Curcumin; Gemini surfactant nanoparticles.

MeSH terms

  • Animals
  • Annexin A5 / pharmacology
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Curcumin* / pharmacology
  • Fluorescein-5-isothiocyanate / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles*
  • Neoplasms* / drug therapy

Substances

  • Curcumin
  • Annexin A5
  • Fluorescein-5-isothiocyanate
  • Antineoplastic Agents