Seyed Isaac Hashemy

Investigating the anticancer effects of chitosan-NLC-folate nanohybrid loaded with auraptene on A2780 ovarian cancer cells

The significant fatality rate associated with ovarian cancer underscores the urgent need for novel therapeutic interventions in this area. The focus of this study was to assess the cytotoxic impact of auraptene nanohybrid chitosan folate on A2780 ovarian cancer cells. A combination of liquid and solid lipids were used to create auraptene-nanostructured lipid carriers. Folic acid was conjugated to chitosan in order to modify the surface. The nanoparticles containing methylene blue were dissolved in deionized distilled water to attach the chitosan-folic acid to the nanoparticles. The resazurin cell viability assay was employed to gauge the cytotoxicity of auraptene on the cells. Real-time PCR was utilized to quantify the expression levels of Bcl-2, Bax, and P53 genes. DLS analysis exposed a spheroidal particle with an approximate diameter of 211 nm. The auraptene nanoparticles did not revealed inhibitory effect on normal cell line (HFF-1) at the concentrations that it was toxic for cancerous cells (A2780). In vitro trials suggested that auraptene nanoparticles trigger apoptosis in A2780 cells in a dose-responsive manner by promoting the expression of pro-apoptotic genes (Bax and P53), while suppressing the expression of the anti-apoptotic gene (Bcl-2). Furthermore, auraptene nanoparticles also heightened the production of reactive oxygen species within the cancerous cells. The notable cytotoxic and lethal influence of auraptene nanoparticles on human ovarian cancer may be attributed to their capacity to generate oxidative stress conditions and induce apoptosis.

Sol-gel synthesis and cytotoxicity evaluation of selenium-doped cerium oxide nanoparticles for biomedical applications

Over the past few years, ovarian cancer is the second most commonly diagnosed cancer among women. Despite the widespread knowledge of its prevalence, the curative measures and survival rates for ovarian cancer have not improved significantly, making it a challenging condition. Nanotechnology has become increasingly prominent in the field of cancer treatment. Previous studies showed both cerium oxide nanoparticles (CONPs) and selenium (Se) had anti-cancer. Therefore, doping selenium into CONPs may exhibit a more significant anti-cancer effect on ovarian cancer cells. Cerium nitrate hexahydrate, sodium selenite, and gelatin were employed for the production of CONPs and Se-doped CONPs. The EDX, XRD, and TEM/PSA imaging were employed to investigate the structural characteristics and morphology of the synthesized Se-doped CONPs. The reactive oxygen species (ROS) level and TNF, IL-6, and IL-1B gene expression were evaluated after inoculating A2780 human epithelial ovarian carcinoma (HEOC) with Se-doped CONP. Statistical analysis was conducted using ANOVA, followed by Bonferroni's t-test for multiple group comparisons. Se-doped CONPs had IC

The Effect of Blocking Neurokinin-1 Receptor by Aprepitant on the Inflammatory and Apoptosis Pathways in Human Ovarian Cancer Cells

Ovarian cancer is the seventh most common cancer globally, and the second most common cancer among women with significant mortality. Toward this end, it is shown that substance P (SP) is involved in tumor initiation and progression through the neurokinin-1 receptor (NK1R). However, the exact molecular mechanism of the SP/NK1R system in ovarian cancer is not yet fully clarified. In this in vitro study, we decided to investigate the effect of the SP/NK1R system and blockage of NK1R by its specific antagonist (Aprepitant) on the proliferation of ovarian cancer cells as well as the alteration of inflammatory pathways. Our results revealed that Aprepitant stimulated apoptotic cell death and attenuated inflammation of ovarian cancer cells through the NF-kB and P53 signaling pathways. After treatment with Aprepitant, the expression of downstream anti-apoptotic genes related to the NF-kB pathway (survivine and bcl2) was decreased. However, we indicated the positive effect of SP on the proliferation of ovarian cancer cells by inducing the expression of NF-kB protein and NF-kB anti-apoptotic target genes. Moreover, Pro-apoptotic p53 target genes (P21 and Bax) were increased through aprepitant treatment, while SP attenuated these genes' expression. Besides, ROS generation in ovarian cancer cells after treatment with SP induced, while blocking of NK1R with Aprepitant reduced the level of ROS generation. Given this, our data suggest that this NK1R might be used as an important therapeutic target in ovarian cancer and Aprepitant could be considered a new drug in ovarian cancer therapy.

The effect of substance P and its specific antagonist (aprepitant) on the expression of MMP-2, MMP-9, VEGF, and VEGFR in ovarian cancer cells

Substance P (SP) has a crucial role in cancer initiation and progression via binding to its specific receptor (NK1R). Various evidence confirmed the overexpression of NK1R and SP in the tissue of multiple cancers, including ovarian cancer. Despite numerous studies, the mechanism of the SP/NK1R system on migration and angiogenesis of ovarian cancer cells has not yet been deciphered. In this study, considering the critical factors in cell migration (MMP-2, MMP-9) and angiogenesis (VEGF, VEGFR), we investigated the possible mechanism of this system in inducing migration and angiogenesis of ovarian cancer cells. First, the resazurin assay was conducted to evaluate the cytotoxic effect of aprepitant (NK1R antagonist) on the viability of A2780 ovarian cancer cells. After that, the impact of this system and aprepitant on the mRNA expression of the factors mentioned above were studied using RT-PCR. Besides, the scratch assay was performed to confirm the effect of the SP/NK-1R system and aprepitant on cell migration. Our results implied that this system induced cell migration and angiogenesis by increasing the mRNA expression of MMP-2, MMP-9, VEGF, and VEGFR. The obtained results from the scratch assay also confirmed the positive effect of this system on cell migration. Meanwhile, the blocking of NK1R by aprepitant suppresses the SP effects on cell migration and angiogenesis. Overall, the SP/NK1R system plays a vital role in ovarian cancer progression, and the inhibition of NK1Rusing aprepitant could inhibit the spread of ovarian cancer cells through metastasis and angiogenesis.

Potential in vitro therapeutic effects of targeting SP/NK1R system in cervical cancer

Cervical cancer, an aggressive gynecological cancer, seriously threatens women's health worldwide. It is recently reported that neuropeptide substance P (SP) regulates many tumor-associated processes through neurokinin-1 receptor (NK1R). Therefore, we used cervical cancer cell line (HeLa) to investigate the functional relevance of the SP/NK1R system in cervical cancer pathogenesis. Cellular proliferation and cytotoxicity were analyzed by colorimetric MTT assay. Quantitative real-time PCR (qRT-PCR) was used to measure mRNA expression levels of desired genes. Cell cycle distribution and apoptosis were evaluated by flow cytometry. A wound-healing assay was employed to assess migration ability. We found that the truncated isoform of NK1R(NK1R-Tr) is the dominantly expressed form of the receptor in Hela cells. We also indicated that that SP increased HeLa cell proliferation while treatment with NK1R antagonist, aprepitant, inhibited HeLa cell viability in a dose and time-dependent manner. SP also alters the levels of cell cycle regulators (up-regulation of cyclin B1 along with downregulation of p21) and apoptosis-related genes (up-regulation of Bcl-2 along with downregulation of Bax) while aprepitant reversed these effects. Aprepitant also induced arrest within the G2 phase of the cell cycle and subsequent apoptosis. Furthermore, SP promoted the migrative phenotype of HeLa cells and increased MMP-2 and MMP-9 expression while aprepitant exposure significantly reversed these effects. Collectively, our results indicate the importance of the SP / NK1R system in promoting both proliferative and migrative phenotypes of cervical cancer cells and suggest that aprepitant may be developed as a novel treatment for combating cervical cancer.