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Gallium Nanoparticle-Mediated Reduction of Brain Specific Serine Protease-4 in an Experimental Metastatic Cancer
Enas M Moustafa1, Marwa Abdelhameed Mohamed, Noura M Thabet
1Radiation Biology Department, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt.
Abstract:
Purpose: Tumor growth and metastasis depend on angiogenesis; therefore, efforts are being made to develop specific angiogenic inhibitors. Gallium (Ga) is the second most common metal ion, after platinum, used in cancer treatment. Its activities are numerous and various. In the present study, we aimed to investigate the effect of Ga on brain metastasis arising from hepatocellular carcinoma (HCC). Materials and methods: Forty experimental rats (divided into 4 groups) received diethylnitrosamine (DEN) at a dose (20 mg/kg.b.wt.; for 6 weeks) to induce HCC and were treated with Ga nanoparticles (GaNPs) with the bacterium Bacillus licheniformis (1mg/kg.b.wt.). Liver functions (alanine aminotransferase; (ALT), aspartate aminotransferase; (AST) and gamma glutamyl transferase; (GGT) and alpha-fetoprotein (AFP)) were assessed with histopathological examination of liver sections to confirm the induction of HCC. In addtion, brain-specific serine protease 4 (BSSP4), extracellular signal-regulated kinase (ERK), a microtubule-associated protein (Tau), vascular endothelial growth factor (VEGF), vascular cells adhesion molecule-1 (VCAM-1), cytochrome P450 (CYP450), lipid peroxidation (MDA) and glutathione-S-transferase (GST) were measured in brain tissue. Results: GaNPs ranged from 5 to 7 nm. HCC was confirmed by elevation in liver enzymes and AFP. Additionally, histopathological examination of liver showed focal area of anaplastic hepatocytes with other cells forming acini associated with fibroblastic cell proliferation. In brain, compared to the DEN alone group, we found that GaNPs modulated brain metastasis by reducing CYP450 and BSSP4 mRNA, and protein expression of p-ERK and p-Tau, and angiogenesis mediators (VEGF and VCAM-1). Also, GaNPs elevated lipid peroxidation and GST activity. Conclusion: It is concluded that GaNPs may prevent metastasis via inhibition of BSSP4 mRNA expression leading to suppression of a variety of growth factors and cell adhesion molecules involved in tumor growth and angiogenesis.
Insights
Gallium nanoparticles (GaNPs) show promise in preventing brain metastasis from liver cancer by inhibiting key molecules involved in tumor growth and blood vessel formation. This study highlights GaNPs
Area of Science:
- Oncology
- Nanomedicine
- Biochemistry
Background:
- Tumor growth and metastasis are critically dependent on angiogenesis, prompting research into targeted angiogenic inhibitors.
- Gallium (Ga), a metal ion utilized in cancer treatment, possesses diverse biological activities.
- Hepatocellular carcinoma (HCC) is a prevalent liver cancer with a significant propensity for metastasis, including to the brain.
Purpose of the Study:
- To investigate the inhibitory effect of Gallium nanoparticles (GaNPs) on brain metastasis originating from hepatocellular carcinoma (HCC) in an experimental rat model.
Main Methods:
- Hepatocellular carcinoma (HCC) was induced in rats using diethylnitrosamine (DEN).
- Rats were treated with Gallium nanoparticles (GaNPs) administered with Bacillus licheniformis.
- Liver function markers (ALT, AST, GGT, AFP) and histopathological liver examinations were performed. Brain tissue analysis included measurements of BSSP4, ERK, Tau, VEGF, VCAM-1, CYP450, MDA, and GST.
Main Results:
- GaNPs, sized 5-7 nm, were synthesized and characterized.
- HCC induction was confirmed by elevated liver enzymes and alpha-fetoprotein (AFP), alongside characteristic histopathological changes.
- In brain tissue, GaNPs significantly modulated metastasis by reducing CYP450 and BSSP4 mRNA, and protein expression of p-ERK and p-Tau. Angiogenesis mediators VEGF and VCAM-1 were also reduced, while lipid peroxidation and GST activity were elevated.
Conclusions:
- Gallium nanoparticles (GaNPs) demonstrate potential in preventing brain metastasis of hepatocellular carcinoma (HCC).
- The mechanism involves the inhibition of BSSP4 mRNA expression, subsequently suppressing growth factors and cell adhesion molecules crucial for tumor progression and angiogenesis.
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