23 research outputs found
Cytotoxic activity of silver nanoparticles prepared from Psidium guajava L. (Myrtaceae) and Lawsonia inermis L. (Lythraceae) extracts
Purpose: To biosynthesize silver nanoparticles (AgNPs) using Psidium guajava L. and Lawsonia inermis L. leaf extracts, and investigate their antioxidant and cytotoxic activities.Methods: The aqueous extracts were prepared by maceration in distilled H2O followed by partitioning with EtOAc. AgNPs were prepared by treating the extracts with 1 mM AgNO3 and then were characterized by UV-vis and FTIR analyses, and transmission electron microscopy (TEM). MTT cytotoxicity and 2,2`-azinobis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) antioxidant assays were used to assess their cytotoxic and antioxidant properties, respectively.Results: AgNPs from P. guajava and L. inermis extracts exhibited good morphological stability and showed moderate antioxidant activity (68.1 and 71.9%, respectively) compared to their extracts. Equipotent cytotoxicity against HCT-116 and MCF-7 cells was observed for AgNPs derived from P.guajava, while AgNPs derived from L. inermis possessed two-fold cytotoxicity compared to their corresponding extracts. Phytochemical analysis of P. guajava afforded pyrogallol, quercetin, quercetin-3-O-β-xylopyranoside, quercetin-3-O-β-arabinopyranoside, and quercetin-3-O-α-rabinofuranoside, while L. inermis afforded lawsone and luteolin.Conclusion: Flavonoids and phenolics play a major role in reducing Ag+ ions, surface coating, antioxidant, and cytotoxic activities of AgNPs. The biocompatible AgNPs produced by L. inermis demonstrate promising cytotoxic activity that could contribute to new cancer treatments
Corrigendum to “Novel spirooxindole based benzimidazole scaffold: In vitro, nanoformulation and in vivo studies on anticancer and antimetastatic activity of breast adenocarcinoma”
This is a critical needed correction. In Fig. 15, the image corresponding to the lung from mouse treated with 25 mg/kg was taken from the same section of the mouse that was treated with 10 mg/kg. The corrected Fig. 15 [Formula presented] Fig. 15. Microscopic pictures of H&E stained lung sections from groups received (A) 4*106 cells/200 μL showing congested blood vessels (red arrows), peribronchial and interstitial aggregation (black arrows) of tumour cells admixed with MNCs. Microscopic pictures of H&E stained lungs sections from treated groups (B) 10 or (c) 25 mg/kg) showing disappeared congestion with decreased numbers of perivascular and interstitial infiltration of tumour cells. Increasing dose of treatment 25 mg/kg was more efficient than 10 mg/kg. Low magnification X: 100 with 100 μm scale bar.</p
Corrigendum to “Novel spirooxindole based benzimidazole scaffold: In vitro, nanoformulation and in vivo studies on anticancer and antimetastatic activity of breast adenocarcinoma”
This is a critical needed correction. In Fig. 15, the image corresponding to the lung from mouse treated with 25 mg/kg was taken from the same section of the mouse that was treated with 10 mg/kg. The corrected Fig. 15 [Formula presented] Fig. 15. Microscopic pictures of H&E stained lung sections from groups received (A) 4*106 cells/200 μL showing congested blood vessels (red arrows), peribronchial and interstitial aggregation (black arrows) of tumour cells admixed with MNCs. Microscopic pictures of H&E stained lungs sections from treated groups (B) 10 or (c) 25 mg/kg) showing disappeared congestion with decreased numbers of perivascular and interstitial infiltration of tumour cells. Increasing dose of treatment 25 mg/kg was more efficient than 10 mg/kg. Low magnification X: 100 with 100 μm scale bar.</p
Corrigendum to “Novel spirooxindole based benzimidazole scaffold: In vitro, nanoformulation and in vivo studies on anticancer and antimetastatic activity of breast adenocarcinoma”
This is a critical needed correction. In Fig. 15, the image corresponding to the lung from mouse treated with 25 mg/kg was taken from the same section of the mouse that was treated with 10 mg/kg. The corrected Fig. 15 [Formula presented] Fig. 15. Microscopic pictures of H&E stained lung sections from groups received (A) 4*106 cells/200 μL showing congested blood vessels (red arrows), peribronchial and interstitial aggregation (black arrows) of tumour cells admixed with MNCs. Microscopic pictures of H&E stained lungs sections from treated groups (B) 10 or (c) 25 mg/kg) showing disappeared congestion with decreased numbers of perivascular and interstitial infiltration of tumour cells. Increasing dose of treatment 25 mg/kg was more efficient than 10 mg/kg. Low magnification X: 100 with 100 μm scale bar.</p
Corrigendum to “Novel spirooxindole based benzimidazole scaffold: In vitro, nanoformulation and in vivo studies on anticancer and antimetastatic activity of breast adenocarcinoma”
This is a critical needed correction. In Fig. 15, the image corresponding to the lung from mouse treated with 25 mg/kg was taken from the same section of the mouse that was treated with 10 mg/kg. The corrected Fig. 15 [Formula presented] Fig. 15. Microscopic pictures of H&E stained lung sections from groups received (A) 4*106 cells/200 μL showing congested blood vessels (red arrows), peribronchial and interstitial aggregation (black arrows) of tumour cells admixed with MNCs. Microscopic pictures of H&E stained lungs sections from treated groups (B) 10 or (c) 25 mg/kg) showing disappeared congestion with decreased numbers of perivascular and interstitial infiltration of tumour cells. Increasing dose of treatment 25 mg/kg was more efficient than 10 mg/kg. Low magnification X: 100 with 100 μm scale bar.</p
Corrigendum to “Novel spirooxindole based benzimidazole scaffold: In vitro, nanoformulation and in vivo studies on anticancer and antimetastatic activity of breast adenocarcinoma”
This is a critical needed correction. In Fig. 15, the image corresponding to the lung from mouse treated with 25 mg/kg was taken from the same section of the mouse that was treated with 10 mg/kg. The corrected Fig. 15 [Formula presented] Fig. 15. Microscopic pictures of H&E stained lung sections from groups received (A) 4*106 cells/200 μL showing congested blood vessels (red arrows), peribronchial and interstitial aggregation (black arrows) of tumour cells admixed with MNCs. Microscopic pictures of H&E stained lungs sections from treated groups (B) 10 or (c) 25 mg/kg) showing disappeared congestion with decreased numbers of perivascular and interstitial infiltration of tumour cells. Increasing dose of treatment 25 mg/kg was more efficient than 10 mg/kg. Low magnification X: 100 with 100 μm scale bar.</p
Costus speciosus J Koenig (Costaceae) exerts anti-proliferative effect on breast cancer cells via induction of cell cycle arrest and inhibition of activity of metalloproteinase-2
Purpose: To Investigate the antiproliferative effect of n-hexane-diethyl ether fraction of Costus speciosus (NP) on triple negative breast cancer (MDA-MB-231) cells, and the mechanism involved.
Methods: Maceration with methanol (CH3OH) was used for extraction of Costus speciosus rhizomes. Chromatographic separation was used to obtain the non-polar fraction (NP) via elution with n-hexane:(C2H5)2O at a volume ratio of 9:1. The cytotoxic effect of NP was evaluated against two breast cancer cell lines i.e., triple negative (MDA-MB-231) and positive ER (MCF-7) employing 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT) assay, and the IC50 values were estimated. Cell cycle was determined with flow cytometry, while the likely mechanism involved in the cytotoxic effect was investigated using comet assay, immunofluorescence, clonogenic and scratch assays, zymography and detection of the antioxidant markers.
Results: NP produced potent cytotoxicity against MDA-MB-231, with IC50 value of 4 ± 0.03 μg/mL, whereas its IC50 for MCF-7 was 27 ± 1.3 μg/mL. It induced apoptosis via cell cycle arrest at G1 phase. Moreover, NP markedly decreased levels of superoxide dismutase (SOD), reduced glutathione (GSH), and matrix metalloprotease-2 (MMP-2), in MDA-MB-231 cells. Moreover, it inhibited cancer cell migration and colony formation.
Conclusion: Non-polar fraction of Costus speciosus (NP) exerted cytotoxic effect on triple negative breast cancer cells (MDA-MB-231) and positive ER (MCF-7). It inhibited cancer cell migration and colony formation. Interestingly, NP arrested the breast cancer cell cycles at sub-G1 phase, inhibited SOD and MMP-2, and decreased GSH levels. It induced apoptosis via DNA damage, downregulation of mutant p53, and over-expressions of the cell cycle inhibitors p21 and p27
Design, Synthesis, and Biological Evaluation of a Novel VEGFR-2 Inhibitor Based on a 1,2,5-Oxadiazole-2-Oxide Scaffold with MAPK Signaling Pathway Inhibition
Over the past few decades, the development of broad-spectrum anticancer agents with anti-angiogenic activity has witnessed considerable progress. In this study, a new series of pyrazolo[3,4-d]pyrimidines based on a phenylfuroxan scaffold were designed, synthesized, and evaluated, in terms of their anticancer activities. NCI-60 cell one-dose screening revealed that compounds 12a–c and 14a had the best MGI%, among the tested compounds. The target fluorinated compound 12b, as the most active one, showed better anticancer activity compared to the reference drug sorafenib, with IC50 values of 11.5, 11.6, and 13 µM against the HepG-2, A2780CP, and MDA-MB-231 cell lines, respectively. Furthermore, compound 12b (IC50 = 0.092 µM) had VEGFR-2-inhibitory activity comparable to that of the standard inhibitor sorafenib (IC50 = 0.049 µM). Furthermore, the ability of compound 12b in modulating MAPK signaling pathways was investigated. It was found to decrease the level of total ERK and its phosphorylated form, as well as leading to the down-regulation of metalloproteinase MMP-9 and the over-expression of p21 and p27, thus leading to subG1 cell-cycle arrest and, thus, the induction of apoptosis. Additionally, compound 12b decreased the rate of wound healing in the absence of serum, in comparison to DMSO-treated cells, providing a significant impact on metastasis inhibition. The quantitative RT-PCR results for E-cadherin and N-cadherin showed lower expression of the neuronal N-cadherin and increased expression of epithelial E-cadherin, indicating the ability of 12b to suppress metastasis. Furthermore, 12b-treated HepG2 cells expressed a low level of anti-apoptotic BCL-2 and over-expressed proapoptotic Bax genes, respectively. Using the DAF-FM DA fluorescence probe, compound 12b produced NO intracellularly as efficiently as the reference drug JS-K. In silico molecular docking studies showed a structural similarity through an overlay of 12b with sorafenib. Interestingly, the drug-likeness properties of compound 12b met the expectations of Pfizer’s rule for the design of new drug candidates. Therefore, this study presents a novel anticancer lead compound that is worthy of further investigation and activity improvement
Down regulation of fatty acid synthase via inhibition of PI3K/AKT/mTOR in ovarian cancer cell line by novel organoselenium pseudopeptide
Ovarian cancer (OC) is the 7th most common cancer in women world-wide and the 3rd most common female cancer. For the treatment of OC, there is no successful therapeutic. The medications that are currently available have significant side effects and a low therapeutic index. This work aimed to evaluate the anticancer activity of organoselenium pseudopeptide compound against OC cell lines. After treatment with 50 μM of compound 4 (CPD 4), the viability was determined. The anticancer activity was further investigated by different methods including cell cycle and apoptosis analysis, colony formation assay, zymography, comet assay and Western blot. In comparison to a positive control, compound 4 showed cytotoxicity toward A2780CP cells rather than A2780 and SKOV-3 cells. Compound 4 was more selective to OC cells rather than HSF cells. Moreover, Compound 4 was able to inhibit cell migration and proliferation. The anticancer effect of compound 4 was found to be partially via cell cycle arrest, overexpression of p27 cell cycle inhibitor and induction of apoptosis through DNA fragmentation and activated production of ROS. Compound 4 had a differential effect on the modulation of PI3K/AKT/mTOR signaling pathway in the OC treated cell lines, also inhibited lipogenesis process via downregulation of FASN expression. Conclusion: This work highlights the unique role of Compound 4 against OC via modulation of oxidative stress, inhibition of survival PI3K/AKT/mTOR pathway. Compound 4 was found to be a promising alternative therapy for the treatment of OC in this investigation
On the Neuroprotective Effects of Naringenin: Pharmacological Targets, Signaling Pathways, Molecular Mechanisms, and Clinical Perspective
As a group of progressive, chronic, and disabling disorders, neurodegenerative diseases (NDs) affect millions of people worldwide, and are on the rise. NDs are known as the gradual loss of neurons; however, their pathophysiological mechanisms have not been precisely revealed. Due to the complex pathophysiological mechanisms behind the neurodegeneration, investigating effective and multi-target treatments has remained a clinical challenge. Besides, appropriate neuroprotective agents are still lacking, which raises the need for new therapeutic agents. In recent years, several reports have introduced naturally-derived compounds as promising alternative treatments for NDs. Among natural entities, flavonoids are multi-target alternatives affecting different pathogenesis mechanisms in neurodegeneration. Naringenin is a natural flavonoid possessing neuroprotective activities. Increasing evidence has attained special attention on the variety of therapeutic targets along with complex signaling pathways for naringenin, which suggest its possible therapeutic applications in several NDs. Here, in this review, the neuroprotective effects of naringenin, as well as its related pharmacological targets, signaling pathways, molecular mechanisms, and clinical perspective, are described. Moreover, the need to develop novel naringenin delivery systems is also discussed to solve its widespread pharmacokinetic limitation