Crystal structure and chemotherapeutic efficacy of the novel compound, gallium tetrachloride betaine, against breast cancer using nanotechnology

Tumour Biol. 2016 Aug;37(8):11025-38. doi: 10.1007/s13277-016-4969-2. Epub 2016 Feb 19.

Abstract

The objective of this study was to investigate the antitumor efficacy of a novel synthesized compound, betaine gallium-tetrachloride (BTG), alone or combined with ZnO-nanoparticles (BTG + ZnO-NPs) on the incidence of 7, 12-dimethylbenz-anthrathene-induced mammary tumor in female rats. Crystal and molecular structure of the prepared BTG were identified using X-ray crystallography. In vitro study revealed BTG more cytotoxic than BTG + ZnO-NPs on human breast cancer (MCF-7) cell line. In vivo study demonstrated that the blood antioxidant status of tumor-bearing rats (DMBA group) was significantly lower than normal noticeable by a significant decrease in GSH content, GPx, SOD, and CAT activities associated with a significantly high MDA content. Both treatments have significantly elevated SOD and CAT activities with a concomitant decrease of MDA level compared to DMBA group. However, BTG + ZnO-NPs accentuated the decrease of GSH regarding DMBA group. The results showed also that both treatments significantly activate caspase-3 enzyme and apoptosis in mammary glands. Their administration to tumor-bearing rats was found to significantly reduce plasma iron and iron-binding capacity (TIBC) compared to DMBA group. Regarding liver function, both treatments significantly reduced the increase of ALT and AST activities compared to DMBA group. However, BTG + ZnO-NPs decreased albumin below normal level. Histopathological studies showed that normalization of tissue structures was higher in BTG than BTG + ZnO-NPs treatment. According to the results obtained, it is observed that the antitumor effect of BTG alone was as strong as BTG + ZnO-NPs and even more efficient in some aspects accordingly, a combination is not needed. Thus, the novel synthetic gallium derivatives may potentially present a new hope for the development of breast cancer therapeutics, which should attract further scientific and pharmaceutical interest.

Keywords: Betaine; Breast cancer; Gallium trichloride; ZnO-nanoparticles.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Betaine / administration & dosage*
  • Betaine / chemical synthesis
  • Betaine / chemistry
  • Crystallography, X-Ray
  • Disease Models, Animal
  • Drug Carriers / pharmacology*
  • Female
  • Gallium / administration & dosage*
  • Gallium / chemistry
  • Humans
  • MCF-7 Cells
  • Mammary Neoplasms, Experimental*
  • Metal Nanoparticles*
  • Nanotechnology / methods
  • Oxidative Stress / drug effects
  • Rats
  • Zinc Oxide / pharmacology

Substances

  • Drug Carriers
  • Betaine
  • Gallium
  • Zinc Oxide