Enhancing the efficacy of letrozole-loaded PEGylated nanoliposomes against breast cancer cells: In vitro study.

Considering its overall impact on human health, letrozole (Let) has been described as having significant efficacy that could be improved by developing drug delivery systems. Considering the side effects of Let, this study aims to encapsulate Let in liposomes and PEGylated liposome nanoparticles (Lipo-Let-PEG) and evaluate the cytotoxic effects on the MCF-7 breast cancer cell line. For this purpose, the Lipo-Let-PEG formulation was designed and characterized by SEM, DLS, and FTIR methods, and the drug release from the optimized formulation and the stability of the optimized Lipo-Let-PEG were measured. Furthermore, the cytotoxicity and apoptotic studies were performed using MTT assay and flow cytometric analysis. According to the experimental data, the vesicle size and EE% were 170.05 ± 4.15 nm and 87.21 ± 1.36 %, respectively. The cumulative release from Lipo-Let-PEG at pH 5.4 and 7.4 was also approximately 60 % and 50 %, respectively. MTT results showed that Lip-Let-PEG produced more drug cytotoxicity than Lip-Let against MCF-7 cancer cells and was more compatible with normal cells. The results of apoptosis and cell cycle arrest using flow cytometry show that Lipo-Let-PEG caused the most significant increase in apoptotic rates and cell cycle arrest in cancer cells compared to other treated groups. In conclusion, Lipo-Let-PEG can be used as an anticancer agent by arresting cell cycle progression and inducing apoptosis, which can be applied in future studies to prevent breast cancer development.

Fabrication, optimization, and characterization of pH-responsive PEGylated nanoniosomes containing gingerol for enhanced treatment of breast cancer.

Multiple potential drug delivery strategies have emerged as a result of recent advances in nanotechnology and nanomedicine. The aim of this research was to prepare an optimized system of PEGylated gingerol-loaded niosomes (Nio-Gin@PEG) as an excellent candidate for the treatment of human breast cancer cells. The preparation procedure was modified by adjusting the drug concentration, lipid content, and Span60/Tween60 ratio, resulting in high encapsulation efficacy (EE%), rapid release rate, and reduced size. The Nio-Gin@PEG exhibited significantly improved storage stability compared to the gingerol-loaded niosomes formulation (Nio-Gin), with minimal changes in EE%, release profile, and size during storage. Furthermore, Nio-Gin@PEG demonstrated pH-dependent release behavior, with delayed drug diffusion at physiological pH and significant drug diffusion under acidic conditions (pH = 5.4), making it a promising option for cancer treatment. Cytotoxicity tests indicated that Nio-Gin@PEG possessed excellent biocompatibility with human fibroblast cells while exerting a remarkable inhibitory effect on MCF-7 and SKBR3 breast cancer cells, attributed to the presence of gingerol and the PEGylated structure in the preparation. Nio-Gin@PEG also exhibited the ability to modulate the expression of target genes. We observed statistically significant down-regulation of the expression of BCL2, MMP2, MMP9, HER2, CCND1, CCNE1, BCL2, CDK4, and VEGF genes, along with up-regulation of the expression of BAX, CASP9, CASP3, and P21 genes. Flow cytometry results revealed that Nio-Gin@PEG could induce a higher rate of apoptosis in both cancerous cells compared to gingerol and Nio-Gin, owing to the optimal encapsulation and efficient drug release from the formulation, as confirmed by cell cycle tests. ROS generation demonstrated the superior antioxidant effect of Nio-Gin@PEG compared to other prepared formulations. The results of this study emphasize the potential of formulating highly biocompatible niosomes in the future of nanomedicine, enabling more precise and effective treatment of cancers.

NGF, BDNF and Arc mRNA Expression in the Hippocampus of Rats After Administration of Morphine.

Morphine can influence immediate early genes (IEG) of activity-regulated cytoskeletal-associated protein (Arc) and brain-derived neurotrophic factor (BDNF) which are activated in response to physiological stimuli during learning, as well as the nerve growth factor (NGF) gene which increases the expression of several IEGs for memory formation. The purpose of the current study was first to evaluate the effect of acute (1-day) and subchronic (15-days) morphine administration on memory retrieval of rats and second to determine the hippocampal expression of NGF, BDNF and Arc genes as potential contributors in the observed effects in each setting. The effects of morphine (intraperitoneal, 10, 15 and 20 mg/kg) on memory function and gene expression were assessed using inhibitory avoidance test and real-time polymerase chain reaction, respectively. We found that a single dose of morphine at the highest dose of 20 mg/kg decreases the post-training step-through-latency, while repeated administration of the same dose for 15 successive days increases this indicator of memory retrieval. We did not detect a significant change in the hippocampal expression of Arc, BDNF or NGF genes after a single episode of morphine treatment. However, subchronic morphine administration (15 and 20 mg/kg) increased the expression of Arc and BDNF genes in a dose dependent manner. A higher mRNA expression for the NGF was observed at the higher dose of 20 mg/kg. We hypothesize that the subchronic effects were morphine-induced behavioral sensitization which may have been enhanced through increased hippocampal Arc expression.

The Effect of Cadmium on Apoptotic Genes mRNA Expression of Bax and Bcl-2 in Small Intestine of Rats.

BACKGROUND & OBJECTIVE: Cadmium is a potent toxicant and carcinogenic substance for human and experimental animals. The evidences indicate that cadmium induces aberrant gene expression, inhibition of DNA damage repair, and apoptosis. In this study, we investigated the effects of IP (intraperitoneal) injection of cadmium on mRNA levels expression of Bcl-2 and Bax genes in rat small intestine. METHODS: 28 male Wistar rats weighing 200 to 250 grams were randomly assigned into 4 groups. Group 1 received saline while the animals in groups 2-4 were injected cadmium (1, 2 and 4 mg/kg) for 15 successive days. One day after the last injection, the small intestine was dissected and the mRNA levels expression of Bax and Bcl-2 genes was evaluated using Real Time PCR technique. RESULTS: Cadmium increased the mRNA levels of Bax gene compared to the control group at 2 and 4 mg/kg (P < 0.01) in small intestine of rats. The mRNA levels of Bcl-2 gene decreased significantly compared to the control group at 1, 2 and 4 mg/kg (P < 0.001) in small intestine of rats. CONCLUSION: These results showed Cadmium exposure induced cell apoptosis by increasing Bax/Bcl-2 ratio expression.

The HER-2 as a Target Gene of Curcumin to Protect Hepatocytes Against the Arsenic-induced Carcinoma in Mice.

BACKGROUND & OBJECTIVE: The HER-2 gene is an important on co protein overexpressed in many types of cancers. The current study hypothesized that curcumin downregulates HER-2 and inhibits the signal transduction pathway of PI3K/Akt, MAPK, and activation of NFκB, which could be useful to treat overexpressed-HER-2 hepatocellular carcinoma (HCC). METHODS: In the current study, 40 male NMRI (Naval Medical Research Institute) mice were divided into 4 groups of 10 as follow: Group1 (control group) only received 5 mL/kg corn oil, group 2 (poisoned group) received 30 mg/L arsenic (As2O3) dissolved in water, group3 (curcumin treated), and group 4 (curcumin and arsenic treated) received 10 to 20mg/5mL/kg for 60 days. Once experimental period was completed, liver samples were collected. The analysis of the gene expression was performed by real-time polymerase chain reaction (PCR) technique. RESULTS: Gene expression analysis showed that curcumin had significantly downregulated the activity of HER-2, in poisoned mice. CONCLUSION: According to the current study results, it could be concluded that curcumin has the inhibitory potential toward HER-2-overexpressed HCC.