Antimicrobial, Antiviral, and In-Vitro Cytotoxicity and Mosquitocidal Activities of Portulaca oleracea-Based Green Synthesis of Selenium Nanoparticles.

The aqueous extract of Portulaca oleracea was used as a biocatalyst for the reduction of Na2SeO3 to form Se-NPs that appeared red in color and showed maximum surface plasmon resonance at a wavelength of 266 nm, indicating the successful Phyto-fabrication of Se-NPs. A FT-IR chart clarified the role of plant metabolites such as proteins, carbohydrates, and amino acids in capping and stabilizing Se-NPs. TEM, SAED, and XRD analyses indicated the formation of spherical, well-arranged, and crystalline Se-NPs with sizes in the range of 2-22 nm. SEM-EDX mapping showed the maximum peaks of Se at 1.4, 11.3, and 12.4 KeV, with weight and atomic percentages of 36.49 and 30.39%, respectively. A zeta potential of -43.8 mV also indicated the high stability of the synthesized Se-NPs. The Phyto-synthesized Se-NPs showed varied biological activities in a dose-dependent manner, including promising activity against pathogenic bacteria and Candida species with varied MIC values in the range of 12.5-50 µg·mL-1. Moreover, the Se-NPs showed antiviral activity toward HAV and Cox-B4, with percentages of 70.26 and 62.58%, respectively. Interestingly, Se-NPs showed a target orientation to cancer cell lines (HepG2) with low IC50 concentration at 70.79 ± 2.2 µg·mL-1 compared to normal cell lines (WI-38) with IC50 at165.5 ± 5.4 µg·mL-1. Moreover, the as-formed Se-NPs showed high activity against various instar larvae I, II, III, and IV of Culex pipiens, with the highest mortality percentages of 89 ± 3.1, 73 ± 1.2, 68 ± 1.4, and 59 ± 1.0%, respectively, at 50 mg L-1. Thus, P. oleracea-based Se-NPs would be strong potential antimicrobial, anti-viral, anti-cancer, and anti-insect agents in the pharmaceutical and biomedical industries.

Oxaliplatin-loaded nanoemulsion containing Teucrium polium L. essential oil induces apoptosis in Colon cancer cell lines through ROS-mediated pathway.

Oxaliplatin (Oxa)-associated adverse side effects have considerably limited the clinical use of the drug in colon cancer therapy. Mutant p53 has diverse mutational profiles in colon cancer, and it influences the potencies of various chemotherapeutic drugs, including Oxa. Thus, it would be highly beneficial to identify an alternative therapeutic strategy that not only reduces the toxicity of Oxa, but also exerts a synergistic effect against colon cancers, regardless of their p53 profiles. The present study was aimed at preparing and optimizing Teucrium polium L. essential oil nanoemulsion (TPO-NANO) and investigating its effect on the sensitivity of colon cancer cells with differences in p53 status (HCT116 wild-type and HT-29 mutant-type) to Oxa. The viability of treated cells was determined and the combination index (CI) was calculated. Morphological changes were determined under inverted microscopy, while percentage apoptosis was assayed using flow cytometry. Intracellular ROS and the protein levels of p53 and Bax were measured. The colony-forming potential of treated cells was determined using colony assay. The size of TPO-NANO was markedly increased from 12.90 ± 0.04 nm to 14.47 ± 0.53 nm after loading Oxa (p ≤ 0.05). The combination (Oxa + TPO-NANO) produced a synergetic effect in HCT116 and HT-29, with CI of 0.94 and 0.88, respectively. Microscopic examination and flow cytometric analysis revealed that cells treated with Oxa + TPO-NANO had a higher percentage of apoptosis than cells exposed to monotherapy. Cumulatively, Oxa exerted an apoptotic effect on wild or mutant p53 colon cancer cells when combined with TPO-NANO, through a mechanism involving ROS-mediated mitochondrial apoptosis.

Gemcitabine-Loaded Nanocarrier of Essential Oil from Pulicaria crispa: Preparation, Optimization, and In Vitro Evaluation of Anticancer Activity.

The limitations of gemcitabine (GEM) in cancer therapy are due to its poor pharmacokinetics, which cause undesired adverse effects. The current study was aimed at investigating the anticancer effect and apoptotic mechanism of synthesized nanoemulsion (NE) containing Pulicaria crispa essential oil (PC-EO) and GEM (PC-NE:GEM) on MCF-7 and Hep-G2 cancer cell lines. An optimized NE formulation was selected based on the Box-Behnken method. The droplet size of the optimized PC-NE was 9.93 ± 0.53 nm, but after GEM loading, it was increased to 11.36 ± 0.0.21 nm. Results from FTIR revealed that GEM was successfully loaded onto PC-NE. The antineoplastic effect of PC-NE:GEM on MCF-7 and Hep-G2 cancer cells was increased more than 100-fold relative to that of GEM. A combination index and isobologram based on CompuSyn software revealed the synergistic effect of the formulation produced by a 1:1 ratio combination of PC-NE and GEM. These findings were confirmed by examination of cellular morphologies. The combination formulation strongly induced about 4.48-fold and 2.95-fold increases in apoptosis in MCF-7 and Hep-G2 cells, respectively, when compared with GEM. Moreover, PC-NE:GEM produced a synergistic increase in ROS production in MCF-7 cells (15.23%) and Hep-G2 cells (31.69%), when compared with GEM. In addition, PC-NE:GEM enhanced the activation of the intrinsic apoptosis pathway through upregulation of expressions of p53 and Caspase-3, and downregulation of Bcl-2 expression in MCF-7 cells, while the expressions of Caspase-3, Bax, and p53 were upregulated in HepG2 cells. These results indicate that the GEM-loaded NE containing PC-EO may reduce the dose of GEM and eliminate the associated side effects.

Incorporating ifosfamide into salvia oil-based nanoemulsion diminishes its nephrotoxicity in mice inoculated with tumor.

Introduction: Nephrotoxicity is one of the major side effects of the chemotherapeutic drug, ifosfamide (IFO). In this study, IFO was solubilized in nanoemulsion (NE) containing salvia (SAL) essential oil to investigate its adverse side effects in mice. Methods: One hundred female Swiss albino mice (n = 20/group) were split into five groups. Group I (Normal) received saline solution (0.9% (w/v) NaCl) while groups II-V were intraperitoneally (I.P.) injected with 2.5 × 106 Ehrlich ascetic carcinoma (EAC) cells/mouse. Group II (EAC) represented the untreated EAC-bearing mice. Group III (IFO) was treated with IFO at a dose of 60 mg/kg/d (I.P. 0.3 mL/mouse). Group IV (SAL) was treated with 0.3 mL blank NE-based SAL oil/mouse. Group V (SAL-IFO) was treated with IFO, loaded in 0.3 mL of blank SAL-NE, at a dose of 60 mg/kg/d (I.P. 0.3 mL/mouse). Groups III-V were treated for three consecutive days. Results: There was a double increase in the survival percentage of the SAL-IFO group (60%) relative to the IFO group (30%). Renal damage with the presence of Fanconi syndrome was indicated in the IFO group through a significant elevation in the levels of serum creatinine, blood urea nitrogen, urine bicarbonate, and phosphate in addition to a reduced level of glucose compared to the normal group. On the other hand, the administration of SAL-IFO into the mice reversed this effect. Additionally, the oxidative stress in the kidney tissues of the SAL-IFO group was ameliorated when compared to the IFO group. Conclusion: Incorporating IFO into SAL-NE has protected the kidneys from the damage induced by IFO.

Incorporation of ifosfamide into various essential oils -based nanoemulsions ameliorates its apoptotic effect in the cancers cells.

The chemotherapeutic drugs, loaded in nanocarriers, have recently attracted the pharmaceutical industries due to their limited adverse side effects. The objective of the current study was to incorporate the ifosfamide (IFO) into two different essential oils-based nanoemulsions, lemon (LEM-IFO) and salvia (SAL-IFO). The antiproliferation activities of the resulted formulas were evaluated in the MCF-7 breast cancer cells and HeLa cervical cancers cells. The cytotoxic effect of the NE formulas was detected by the MTT assay, DAPI stain and light microscopy. The z-average diameters range of LEM-IFO and SAL-IFO, determined by the zetasizer, were 49.15-61.81 nm and 56.64-64.62 nm, respectively. The half maximal inhibitory concentration (IC50) of LEM-IFO and SAL-IFO, applied into the HeLa cells, were 0.165 ± 0.025 and 0.141 ± 0.035 mM, respectively, whereas the IC50 of LEM-IFO and SAL-IFO subjected into the MCF-7 cells were 0.200 ± 0.005 mM and 0.270 ± 0.025 mM, respectively. The IC50 of the free IFO was markedly larger than LEM-IFO and SAL-IFO when applied into MCF-7 cells (9.20 ± 2.01 mM) and HeLa cells (7.69 ± 1.88 mM). Among the tested formulas, LEM-IFO and SAL-IFO have the greatest apoptotic effect on the MCF-7 and HeLa cells, respectively. Solubilizing the IFO in the essential oils-based NE has ameliorated the antitumor efficacy of IFO.

Genetic polymorphism and expression of HSF1 gene is significantly associated with breast cancer in Saudi females.

The transcription factor, heat shock factor 1 (HSF1), influences the expression of heat shock proteins as well as other activities like the induction of tumor suppressor genes, signal transduction pathway, and glucose metabolism. We hypothesized that single nucleotide polymorphisms (SNPs) in HSF1 gene might affect its expression or function which might have an influence on the development of breast cancer. The study group included 242 individuals (146 breast cancer patients and 96 healthy controls). From the cancer patients, genomic DNA was extracted from 96 blood samples and 50 Formalin-Fixed Paraffin Embedded (FFPE) tissues, while from the controls DNA were extracted from blood only. Genotype was carried out for four SNPs in the HSF1 gene (rs78202224, rs35253356, rs4977219 and rs34404564) using Taqman genotyping assay method. The HSF1 expression was investigated using immunohistochemistry on FFPE tissues (cancer tissue and adjacent normal tissue). The SNP rs78202224 (G>T) was significantly associated with increased risk of breast cancer. The combined TT + GT genotype (OR: 6.91; p: 0.035) and the T allele showed high risk (OR: 5.81; p:0.0085) for breast cancer development. The SNP rs34404564 (A>G) had a protective effect against the development of breast cancer. The genotype AG (OR: 0.41; p = 0.0059) and GG+AG (OR: 0.52; p: 0.026) occurred at a significantly lower frequency in the breast cancer patients compared to the frequency in healthy controls. No significant relationship was identified between either rs35253356 (A>G) or rs4977219 (A>C) and breast cancer in Saudi. The HSF1 protein expression was higher in all invasive and in situ breast carcinoma compared to the normal tissue. A stronger positive staining for HSF1 was found in the nucleus compared to the cytoplasm. Our results show that HSF1 gene expression is elevated in breast cancer tissue and two of the studied SNPs correlate significantly with cancer development.