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Published on: November 10, 2013
Evaluation of Silver Nanoparticles Caffeic Acid Complex Compound as New Potential Therapeutic Agent against Cancer
Tahany Saad Abdelwahab1, Rania Ellisy Abdelhamed1, Eman Noaman Ali2
1Department of chemistry, Faculty of Science, Helwan University, Egypt.
Objective:
The present work was designed to study the effect of new conjugated caffeic and folic acid with silver nanoparticles with definite molecular size applied with and without gamma radiation exposure, as an antitumor agent against experimentally induced Ehrlich tumor and attempted to identify their potential molecular mechanisms of action throughout determination of anti-tumor activities using MTT cytotoxic assay against two human carcinoma cell lines in vitro, such as apoptosis analysis by flow cytometry through caspase-8, caspase-3 and TNF determination in vivo.
Materials And Methods:
Adult female albino mice were used and divided into five groups. Animals were sacrificed and the following parameters were estimated, glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) in blood in addition to caspase8, caspase 3 and tumor necrosis factor (TNF) of tumor tissue, liver and kidney function also measured in plasma. The tumor specimens were processed for histopathological examination.
Results:
Nano-silver folate caffeic (NSFC) complex compound treatment resulted in growth inhibition in Ehrlich solid tumor, Hep-G2, and MCF-7 cells (IC50 0.062 mg, 7.70 µM, and 14.50 µM, respectively). Flow cytometric analysis revealed that (NSFC) with radiation IR had apoptotic effects at caspases 8 (Mean±SD) (49.4±14), caspase3 (39.97±9.75), and TNF (40.1±3.4) more than any other groups. Those disturbances were found to be associated with a kinetic induction of apoptosis and showed modulation of the antioxidant system {glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) which were 60.70±0.80, 26.73±0.80, 39.52±0.58 respectively}at the group which took (NSFC+IR), besides its high percentage of necrotic cells by histopathological studies. In conclusion, the present study showed that the treatment of (NSFC) exhibits very efficient oncolytic activity in delaying tumor growth in mice bearing Ehrlich Solid Carcinoma (ESC) and the mechanisms underlying the inhibitory effect of the present compound involve both an apoptotic effect against Hep-G2 and MCF-7 cells and modulation of antioxidant system.
Insights
New nano-silver folate caffeic (NSFC) complex effectively inhibits tumor growth by inducing apoptosis and modulating the antioxidant system. This novel antitumor agent shows significant potential in delaying tumor progression in vivo and in vitro.
Area of Science:
- Nanotechnology in Medicine
- Cancer Research
- Molecular Biology
Background:
- Silver nanoparticles conjugated with caffeic and folic acid offer a novel approach for cancer therapy.
- Understanding the molecular mechanisms of antitumor agents is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the antitumor efficacy of a new nano-silver folate caffeic (NSFC) complex, with and without gamma radiation.
- To elucidate the molecular mechanisms underlying the antitumor activity of NSFC, focusing on apoptosis and the antioxidant system.
Main Methods:
- In vitro cytotoxicity assessment using MTT assay on human carcinoma cell lines (Hep-G2, MCF-7).
- In vivo studies using Ehrlich solid tumor model in mice.
- Flow cytometry analysis of apoptosis markers (caspase-8, caspase-3) and TNF.
- Biochemical assays for antioxidant parameters (GSH, GPx, SOD) and histopathological examination of tumor tissues.
Main Results:
- NSFC demonstrated significant growth inhibition against Ehrlich solid tumor, Hep-G2, and MCF-7 cells.
- Combined NSFC and gamma radiation (IR) induced significant apoptosis, evidenced by elevated caspase-8, caspase-3, and TNF levels.
- NSFC+IR treatment modulated the antioxidant system, increasing GSH, GPx, and SOD levels, and led to a high percentage of necrotic cells.
- Histopathological studies confirmed NSFC's oncolytic activity and induction of necrosis.
Conclusions:
- The NSFC complex exhibits potent oncolytic activity against Ehrlich Solid Carcinoma in mice.
- The antitumor mechanisms involve the induction of apoptosis in cancer cells and modulation of the host's antioxidant system.
- NSFC, particularly when combined with gamma radiation, represents a promising therapeutic strategy for cancer treatment.
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