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1.
J Funct Biomater ; 13(3)2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36135592

RESUMO

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.

2.
Drug Deliv ; 29(1): 2190-2205, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35815706

RESUMO

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.


Assuntos
Neoplasias do Colo , Óleos Voláteis , Teucrium , Apoptose , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Células HCT116 , Células HT29 , Humanos , Óleos Voláteis/farmacologia , Oxaliplatina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Teucrium/metabolismo , Proteína Supressora de Tumor p53/metabolismo
3.
Pharmaceutics ; 14(7)2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35890232

RESUMO

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.

4.
Anticancer Agents Med Chem ; 19(10): 1232-1242, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30961514

RESUMO

PURPOSE: The present study aimed to investigate the antitumor activity and hepatoprotective effect of the MTC, when combined with CHAM oil nanoemulsion (NE), (CHAM-MTC) on the tumor growth. MATERIALS/METHODS: The in vitro study assessed the antineoplastic effect of CHAM-MTC on the MCF-7 breast cancer cells while the in vivo therapeutic effectiveness and toxicities of CHAM-MTC were evaluated in Ehrlich Ascites Carcinoma (EAC) bearing mice. One hundred female Swiss albino mice, divided equally into non-EAC group (negative control), untreated EAC group (positive control) and three EAC groups received once intraperitoneal injection of 0.2ml CHAM-NE, 0.2ml Normal Saline (NS) contained MTC (1mg/kg) and 0.2ml CHAM-NE mixed with MTC (1mg/kg), respectively. RESULTS: The in vitro results indicated that CHAM-NE could potentiate the effect of MTC in sub-effective concentrations since the half-maximal inhibitory concentration (IC50) was reduced by a factor of 21.94 when compared to the MTC-NS. The in vivo study revealed that mice treated with CHAM-MTC showed a significant increase in the median survival time (MST= 37 days) when compared to the MTC-NS treated group (MST= 29.50 days). In addition, CHAM-MTC showed protective ability against the oxidative stress and hepatic damage induced by EAC and MTC treatment. CONCLUSION: The combination of MTC with CHAM-NE could be valuable in enhancing the therapeutic efficacy of MTC against EAC and in eliminating MTC-induced hepatotoxicity.


Assuntos
Antineoplásicos Fitogênicos/química , Camomila/química , Emulsões/química , Mitomicina/química , Nanocápsulas/química , Óleos de Plantas/química , Animais , Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Células MCF-7 , Camundongos , Mitomicina/farmacologia , Óleos de Plantas/farmacologia
5.
Biomed Pharmacother ; 106: 946-955, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30119267

RESUMO

The present study aimed to solubilize the antineoplastic agent, mitomycin C (MMC), in two nanoemulsions (NEs) consisting of different essential oils (ginger (Gi) and frankincense (Fr)) in order to examine their anticancer activities on the HeLa cervical cancer cells and MCF-7 breast cancer cells. The two NEs-based Gi and Fr oil were produced by a high-pressure homogenization technique followed by solubilizing of the MMC in both NE formulas. The produced formulas were physically characterized by zetasizer and were applied on HeLa and MCF-7 cells at various concentrations for 24 h. The cytotoxicity assays were performed in vitro, using MTT assay, Coomassie blue staining for cellular morphology evaluation, and DAPI fluorescent staining for molecular cell death assessment. The average droplet diameters of the blank NEs have markedly increased and the charges of the droplets were significantly reversed when MMC was loaded. The potential cytotoxicity of the blank and combined formulas on HeLa and MCF-7 cells were dose-dependent and significantly greater than the toxicities of the free MMC. Among the MMC-loaded NE formulas, Fr-MMC has endured the nuclear apoptosis in HeLa cells at a lower concentration and reported the least % of florescence uptake compared to Gi-MMC. In contrast, the combination formula, Gi-MMC, has the strongest apoptotic effect on the MCF-7 cell line since it has the least % florescence uptake compared to the other formulations. Mixing MMC with Gi-NE and Fr-NE has considerably improved its cytotoxicity on the MCF-7 and HeLa cells.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Franquincenso/farmacologia , Mitomicina/farmacologia , Nanopartículas , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/química , Neoplasias da Mama/patologia , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Composição de Medicamentos , Emulsões , Feminino , Franquincenso/química , Zingiber officinale , Células HeLa , Humanos , Células MCF-7 , Mitomicina/química , Óleos Voláteis/química , Óleos de Plantas/química , Solubilidade , Neoplasias do Colo do Útero/patologia
6.
Chem Biol Interact ; 291: 72-80, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29908166

RESUMO

Combining the essential oils (ESSOs) with the chemotherapeutic agent, mitomycin C (MMC), in nanoparticle can be beneficial in cancer therapy. The aim of the current study was to in vitro evaluate the antineoplastic effect of MMC, formulated in two different nanoemulsions (NE) based on two ESSOs, chamomile (Ch) and garlic (Gar), on HeLa cervical cancer cells. The z-average diameter of Ch-NE has slightly increased from 83.39 ±â€¯12.85 nm to 91.18 ±â€¯5.79 nm when mixed with MMC (Ch-MMC) whereas the z-average diameter of Gar-NE has markedly increased from 50.6 ±â€¯1.96 nm to 75.64 ±â€¯7.13 nm when loaded with MMC (Gar-MMC). The zeta potentials of both of Ch-NE and Ch-MMC, which were -1.91 ±â€¯4.38 mV and -5.44 ±â€¯5.26 mV, respectively, have differed from Gar-NE and Gar-MMC, which were 11.4 ±â€¯2.29 mV and 11.5 ±â€¯2.28 mV, respectively. Compared to MMC solution, the cell viabilities of HeLa cells, measured by the MTT assay, were reduced 42 and 20 times when subjected into Ch-MMC and Gar-MMC, respectively. The light microscopy images revealed that the cell membrane of the HeLa cells treated with Gar-NE or Gar-MMC were more altered relative to the cells treated with Ch-NE or Ch-MMC. In contrast, the nuclei of the HeLa cells, stained with DAPI and treated with Ch-NE or Ch-MMC, were more fragmented than the cells treated with Gar-NE or Gar-MMC, indicating that both of Ch-NE and Ch-MMC have passed the cell membrane and affected the nucleus directly whereas Gar-NE and Gar-MMC have got attached to the cell membrane causing damage to the cell. In conclusion, combining MMC with NE-based ESSOs has increased the cytotoxic effect of the MMC on the HeLa cells with different mechanism of actions.


Assuntos
Antineoplásicos/farmacologia , Emulsões/química , Mitomicina/farmacologia , Nanopartículas/química , Óleos Voláteis/farmacologia , Neoplasias do Colo do Útero/patologia , Apoptose/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Forma Celular/efeitos dos fármacos , DNA/metabolismo , Feminino , Células HeLa , Humanos , Nefelometria e Turbidimetria , Transição de Fase , Coloração e Rotulagem , Temperatura
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