Fig. 5. The antioxidant properties of VNPs@Salvia officinalis and BHT against DPPH.
In the process of apoptosis, dangerous, damaged, and unwanted cells are removed without damaging the surrounding tissues or cells. Cancer cells escape from programmed death, one of the reasons for which is the convert in the gene expression that is involved in the process regulation. Most anticancer agents exert their remedial activities by inducing apoptosis [27-31]. Programmed death induction is a main important method to kill tumor cells without complications. In recent research, by the MTT colorimetric method, it was indicated that nanoparticles have a concentration-dependent lethal activity on tumor cells. In addition, it was found that nanoparticles increased apoptosis in cancer cells. Today, the focus of cancer studies is the search for anti-cancer agents with a higher safety factor and greater acceptability for patients. In addition, nanoparticles can act synergistically or redundantly in combination with radiation therapy or chemotherapy for anticancer activity [31-33]. With the advent of nanotechnology, the paradigm of drug delivery systems has been developed, which can carry many drugs with chemical properties and actively target specific cells. Also, it can pass through biological barriers and transfer its cargo to the target location without pharmaceutical interventions. Today, the development of nanoparticles as effective drug carriers is at the center of attention. In these effective carriers, the drug is at the center of attention [33-35]. In this study, nanoparticles were used for cytotoxic purposes by the MTT method. One of the reasons that nanoparticles had a significant effect on cancer cells is that this phenomenon is due to their direct effect on the cell’s respiratory system in the mitochondria. Therefore, due to the high level of mitochondrial activity in the respiration process of cancer cells compared to normal cells, a suitable substrate is provided for nanoparticles to destroy cancer cells. Another reason is the morphological differences between the membranes of cancer cells in terms of the size of their pores [35-40]. Various researches have been conducted to investigate the cytotoxic activities of nanoparticles on cancer cell lines [38-40]. The results of this study showed that metal nanoparticles in low concentrations do not have significant cytotoxic effects, but in higher concentrations, they have significant cytotoxic effects. The results of this research showed that the cytotoxicity of nanoparticles is dependent on dose and time and suggested that this nanoparticle can have biomedical applications. In general, the results of our study are consistent with other studies in the field of cytotoxicity of nanoparticles. Another mechanism of cytotoxicity of nanoparticles is the toxic oxygen radical’s generation [38-41]. Another mechanism of nanoparticles cytotoxicity is the toxic oxygen radicals (ROS) generation that disturb the cellular redox balance, which is called oxidative stress. Oxidative stress destroys cellular antioxidant enzymes, destruction of cellular DNA structure, oxidation of cellular proteins and membrane lipids, and finally cell death. One of the important issues in the field of using metal nanoparticles in cancer treatment is the non-toxicity of nanoparticles on normal cells [29-34]. Studies show that nanoparticles have a greater effect on cancer cell lines, which is due to their direct effect on the cell’s respiratory system in the mitochondria. Therefore, due to the high level of mitochondrial activity in the respiration process of cancer cells compared to normal cells, a suitable platform is provided for nanoparticles to destroy cancer cells [24-28]. Another reason is the morphological differences between the membrane of normal and cancer cells in terms of the difference in the size of their pores. Also, the difference in the shape, size and surface charge of nanoparticles is another factor in the difference in toxicity of nanoparticles between cancer and normal cells [28-31]. It is important to identify the importance of the apoptotic genes expression pattern in response to the anticancer drugs metastasis activity. Therefore, more investigations are necessary to prove that the mRNA expression profile of this gene can be in response to treatment [27-31]. The results obtained from this study showed the therapeutic use of nanoparticles in cancer cells. According to these reviews, clinical studies on human and animal models are necessary to prove the effect of nanoparticles and also the effect of these nanoparticles on healthy and normal cell lines. So, the nanoparticle’s use can be efficient in enhancing the expression of some proliferative and apoptotic genes [32-36]. According to this study and previous research, it can be concluded that nanoparticles have powerful anticancer effects on cancer cells and derivatives of this compound can be used in the treatment of cancer. Therefore, if the clinical process of this nanoparticle is confirmed, these nanoparticles can be used in clinical cases for cancer patients in the future.
In this study, the treated cells with different concentrations of the present VNPs@Salvia officinalis were assessed by MTT assay for 48h about the cytotoxicity properties on normal (HUVEC) and colorectal malignancy cell lines i.e. Caco-2, COLO 320, DLD-1‎, HCT-15‎, HCT-116‎, and HT-29. The absorbance rate was evaluated at 570 nm, which represented viability on normal cell line (HUVEC) even up to 1000μg/mL for VNPs@Salvia officinalis (Table 1 and Figures 6-9).
The viability of malignant colorectal cell lines reduced dose-dependently in the presence of VNPs@Salvia officinalis . The IC50 of VNPs@Salvia officinalis were 213, 210, 297, 204, 160, and 125 µg/mL against Caco-2, COLO 320, DLD-1‎, HCT-15‎, HCT-116‎, and HT-29 cell lines, respectively (Table 1 and Figures 6-9).