scholarly journals Anticancer Effects of New Ceramides Isolated from the Red Sea Red Algae Hypnea musciformis in a Model of Ehrlich Ascites Carcinoma: LC-HRMS Analysis Profile and Molecular Modeling

Marine Drugs ◽  
2022 ◽  
Vol 20 (1) ◽  
pp. 63
Author(s):  
Sameh S. Elhady ◽  
Eman S. Habib ◽  
Reda F. A. Abdelhameed ◽  
Marwa S. Goda ◽  
Reem M. Hazem ◽  
...  

Different classes of phytochemicals were previously isolated from the Red Sea algae Hypnea musciformis as sterols, ketosteroids, fatty acids, and terpenoids. Herein, we report the isolation of three fatty acids—docosanoic acid 4, hexadecenoic acid 5, and alpha hydroxy octadecanoic acid 6—as well as three ceramides—A (1), B (2), and C (3)—with 9-methyl-sphinga-4,8-dienes and phytosphingosine bases. Additionally, different phytochemicals were determined using the liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (LC-ESI-HRMS) technique. Ceramides A (1) and B (2) exhibited promising in vitro cytotoxic activity against the human breast adenocarcinoma (MCF-7) cell line when compared with doxorubicin as a positive control. Further in vivo study and biochemical estimation in a mouse model of Ehrlich ascites carcinoma (EAC) revealed that both ceramides A (1) and B (2) at doses of 1 and 2 mg/kg, respectively, significantly decreased the tumor size in mice inoculated with EAC cells. The higher dose (2 mg/kg) of ceramide B (2) particularly expressed the most pronounced decrease in serum levels of vascular endothelial growth factor -B (VEGF-B) and tumor necrosis factor-α (TNF-α) markers, as well as the expression levels of the growth factor midkine in tumor tissue relative to the EAC control group. The highest expression of apoptotic factors, p53, Bax, and caspase 3 was observed in the same group that received 2 mg/kg of ceramide B (2). Molecular docking simulations suggested that ceramides A (1) and B (2) could bind in the deep grove between the H2 helix and the Ser240-P250 loop of p53, preventing its interaction with MDM2 and leading to its accumulation. In conclusion, this study reports the cytotoxic, apoptotic, and antiangiogenic effects of ceramides isolated from the Red Sea algae Hypnea musciformis in an experimental model of EAC.

2011 ◽  
Vol 66 ◽  
pp. 0367 ◽  
Author(s):  
H. H. Ahmed ◽  
M. M. Hegazi ◽  
H. I. Abd-Alla ◽  
E. F. Eskander ◽  
M. S. Ellithey

2020 ◽  
Vol 19 ◽  
pp. 153303382092659
Author(s):  
Eman N. Hafez ◽  
Fatma S. M. Moawed ◽  
Gehan R. Abdel-Hamid ◽  
Nermeen M. Elbakary

Purpose: Pathological angiogenesis and apoptosis evasions are common hallmarks of cancer. A different approach to the antitumor effect of parasitic diseases caused by certain protozoans and helminthes had been adopted in recent years as they can affect many cancer characteristics. The present work is an attempt to assess the effect of gamma radiation-attenuated Toxoplasma gondii ME49 as an antiapoptotic and angiogenic regulator modifier on tumor growth aimed at improving cancer protective protocols. Methods: Attenuated Toxoplasma gondii ME49 was administered orally to mice 2 weeks before inoculation with Ehrlich ascites carcinoma to allow stimulation of the immune response. Hepatic histopathology and immune responses were determined for each group. Results: Marked suppression of the tumor proliferation with induction of long-lasting immunity by stimulating interferon γ and downregulating transforming growth factor β. The level of tumor promoting inflammatory markers (STAT-3 and tumor necrosis factor α), the angiogenic factors (vascular endothelial growth factor A, integrin, and matrix metallopeptidase 2 and matrix metallopeptidase 9), as well as nitric oxide concentration were significantly decreased. This was collimated with an improvement in apoptotic regulators (cytochrome-c, Bax, Bak, and caspase 3) in liver tissues of vaccinated mice group compared to Ehrlich ascites carcinoma-bearing one. Moreover, the histopathological investigations confirmed this improvement. Conclusion: Hence, there is an evidence of potency of radiation attenuated Toxoplasma vaccine in immune activation and targeting tumor cell that can be used as a prophylactic or an adjuvant in combination with chemotherapeutic drugs.


1965 ◽  
Vol 43 (7) ◽  
pp. 977-991 ◽  
Author(s):  
P. G. Scholefield

The oxidation of leucine-1-14C to14CO2by Ehrlich ascites carcinoma cells was inhibited on addition of pyruvate and other α-keto acids, a maximum inhibitory effect being attained with 1 mM pyruvate. The only compound, among those tested, which reversed this inhibition was malonate. Oxidation of leucine-2-14C to14CO2occurred at a rate which was 1% of that observed with leucine-1-14C and was sensitive to the presence of fatty acids as well as to pyruvate. Glutamine was a particularly effective inhibitor of leucine oxidation. The inhibition produced by isoleucine was competitive, the KIvalue being 0.13 mM compared with the KMvalue of 0.2 mM. It is suggested that the inhibition by pyruvate is due to a competition between pyruvate and the α-ketoisovaleric acid derived from leucine for the cofactors required for the oxidation of the α-keto acids. In contrast, oxidation of leucine-1-14C by mouse liver slices was increased approximately threefold by pyruvate.


2016 ◽  
Vol 9 (1) ◽  
pp. 20
Author(s):  
Faten Zahran ◽  
Akaber T. Keshta ◽  
Abd El-Shafey I. Ahmed

Purpose: N-halamines were known for their antimicrobial action due to the presence of halogen in their structure. In our search for new anti-cancer agents, we have evaluated the anti-cancer and anti-oxidant properties of some synthetic N-Halamines with high and low molecular weight in comparison with their non-halogenated forms. Urea epichlorohydrin copolymer (1), 4(1H, 3H-2, 6-dioxo-1, 3, 5-trizenyl)-O-iminomethylpolyethylene (3) and cynuric acid (5) in addition to their halogenated forms 2, 4 and 6 were selected for this study. Methodology: the toxicity for the synthesized compounds was determined. The anti-cancer and anti-oxidant activities were studied by evaluation the viability of tumor cells, life span prolongation, and estimation of antioxidants, and effects of these compounds on liver histology. Findings: Doses up to 2000 mg/kg indicated good safety in all investigated compounds. In Vivo antitumor activity results against Ehrlich ascites carcinoma (EAC) cells for the investigated compounds revealed that, the volume of ascites was significantly decreased in compounds 1, 2, 3, 4, 5 and 6 treated groups. EAC cell count was significantly reduced for similar groups, respectively, compared to the positive control group. Malonadildehyde, and nitric oxide showed a significant reduction in their levels in the treated groups, while catalase showed a significant elevation in its activity in the same groups compared to positive control group. Conclusion: Halogenated compounds showed good anti-oxidant behavior while compound 6 showed the best anti-tumor effect.


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