Magnetite Nanoparticles Inhibit Tumor Growth and Upregulate the Expression of P53/P16 in Ehrlich Solid Carcinoma Bearing Mice

Abstract

BackgroundMagnetite nanoparticles (MNPs) have been widely used as contrast agents and have promising approaches in cancer treatment. In the present study we used Ehrlich solid carcinoma (ESC) bearing mice as a model to investigate MNPs antitumor activity, their effect on expression of p53 and p16 genes as an indicator for apoptotic induction in tumor tissues.MethodMNPs coated with ascorbic acid (size: 25.0±5.0 nm) were synthesized by co-precipitation method and characterized. Ehrlich mice model were treated with MNPs using 60 mg/Kg day by day for 14 injections; intratumorally (IT) or intraperitoneally (IP). Tumor size, pathological changes and iron content in tumor and normal muscle tissues were assessed. We also assessed changes in expression levels of p53 and p16 genes in addition to p53 protein level by immunohistochemistry.ResultsOur results revealed that tumor growth was significantly reduced by IT and IP MNPs injection compared to untreated tumor. A significant increase in p53 and p16 mRNA expression was detected in Ehrlich solid tumors of IT and IP treated groups compared to untreated Ehrlich solid tumor. This increase was accompanied with increase in p53 protein expression. It is worth mentioning that no significant difference in expression of p53 and p16 could be detected between IT ESC and control group.ConclusionMNPs might be more effective in breast cancer treatment if injected intratumorally to be directed to the tumor tissues.

The Effect of Vitamin a on Ehrlich Ascites Carcinoma Growth and the Expression of P53, P16, Tert and Vegfas Cancer-Related Genes in Mice.

“…The results of the study have demonstrated that treatment by vitamin A and olive oil has no prevention or productive effect. These results are in agreement with [15]who reported that P16 and P53have important roles in the inhibition of cell proliferation via cell cycle arrest and apoptosis. They are mutated in many tumor cell types [16].Human telomerase reverse transcriptase TERT, which regulates telomere length and can promote tumor development, increases the anti-apoptotic capacity of cells and enhance repair.…”

“…However, our results are in agreement with more recent studies, which showed that high levels of these supplement may increase cases of gastrointestinal cancers, such as stomach, colon, and esophageal, in some populations. [15] In the current study, although there were no significant decrease in the final CT between the olive oil and vitamin treated groups and tumor untreated group,P16and P53 expression levels were increased with olive oil and vitamin A treated groups (decreased TC) compared to tumor untreated group (maximum TC). The results of the study have demonstrated that treatment by vitamin A and olive oil has no prevention or productive effect.…”

“…Some people are advised by their doctors or dietitian to take dietary supplements especially if they have certain medical conditions such as pregnancy or those who have a restricted dietary intake. Many people also take vitamins and supplements while they are being treated for cancer; others take them to prevent cancer.Cancer patients are increasingly turning to supplements to strengthen their immune systems and ease nausea from chemotherapy [15].Until now, the role of vitamin supplements in preventing breast cancer remains unclear.Contradictory data regard beneficial versus unwanted potentiating carcinogenic effect of vitamin A. Epidemiological studies have suggested an inverse correlation between cancer development and dietary consumption of vitamin A.Our results indicated that vitamin A administration before and after the injection of the EAC cells increased, the BW and TC, these results are in disagreement with a study who suggested that the pharmacological concentrations of vitamin A decrease the incidence of chemically induced experimental tumors [16]. Also other studies reported that natural and synthetic retinoid have been demonstrated to inhibit the growth and the development of different types of tumors, including skin, breast, oral cavity, lung, hepatic, gastrointestinal, prostatic, and bladder cancers [17][18].…”

“…The housekeeping gene glyceraldehyde 3-phosphate dehydrogenase (GADPH) was used as an internal control gene to determine the effect of treatment strategies on the expression of P16, P53, TERT and VEGFAgenes. The relative expression of target genes wascomputed based on theirqRT-PCR [15].The sequences of the forward and reverse primes are shown in table (1).The qRT-PCR program was run as follows; at 95 o C for 3 min (activation) and 40 cycles at 95 o C for 15 sec,58 o C for 1 min (annealing) and 60 o C for 1 min (extension). The results of these genes were normalized to GAPDH.…”

Recent Progress of Nanomedicine in the Treatment of Central Nervous System Diseases

“…As we all know, one of the main challenges in disease treatment is how to manipulate drugs toward a particular site. Although there have been some promising strategies, it is hard for drugs to reach to the lesion precisely . Fortunately, magnetic NPs (MNPs) enable the targeted delivery of drugs in vitro and in vivo …”