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

Abstract

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.

Silver Nanoparticles Formulation of Flower Head’s Polyphenols of Cynara scolymus L.: A Promising Candidate against Prostate (PC-3) Cancer Cell Line through Apoptosis Activation

“…So, many scientific papers were oriented to illustrate how these plants undergo their pharmacological effects. Previous studies involved green medicine as a crude extract of the whole plant [ 3 , 4 ], an extract of certain parts [ 5 , 6 ], purified natural compounds [ 7 , 8 , 9 ], or isolated certain bioactive fractions such as polyphenols, essential oils, saponins, alkaloids, polysaccharides, etc. [ 10 , 11 , 12 , 13 , 14 ].…”

Marine natural products

“…354 Other structures were put forward although these were inconsistent with the spectroscopic data provided and are not shown here. 355…”

Biological Review on Different parts of Cynara scolymus L.

“…So, many scientific papers were oriented to illustrate how these plants undergo their pharmacological effects. Previous studies involved the green medicine as a crude extract of whole plant , Eltamany et al, 2022, an extract of certain parts (Goda et al, 2022, Duan et al, 2020, purified natural compounds , Habib et al, 2022 or isolated certain bioactive fractions such as polyphenols, essential oils, saponins, alkaloids & polysaccharides (Micale et al, 2020, Selim et al, 2022. Previous study reported the ability of C. scolymus L. to reduce fasting blood glucose level, A1C-derived average glucose (ADAG), and homeostatic model assessment (HOMA), that assess β-cell function and insulin resistance, in prediabetic patients (Rondanelli et al, 2013).…”