Browsing by Author "Simmet T."

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Acovenoside A Induces Mitotic Catastrophe Followed by Apoptosis in Non-Small-Cell Lung Cancer Cells
(American Chemical Society, 2017) El Gaafary M.; Ezzat, Shahira M; El Sayed A.M.; Sabry O.M.; Hafner S.; Lang S.; Schmiech M.; Syrovets T.; Simmet T.; Department of Pharmacognosy; College of Pharmacy; Cairo University; Giza; 11562; Egypt; Pharmacognosy Department; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA); Cairo; 11562; Egypt; Institute of Pharmacology of Natural Products and Clinical Pharmacology; Ulm University; Ulm; D-89081; Germany
We investigated the cytotoxic potential of the cardenolide glycoside acovenoside A against non-small-cell lung cancer cells. Lung cancer is the leading cause of cancer-related mortality and the second most common cancer diagnosed. Epidemiological studies revealed a direct correlation between the regular administration of cardiac glycosides and a lower incidence of various cancers. Acovenoside A, isolated from the pericarps of Acokanthera oppositifolia, potently inhibited proliferation and induced cytotoxicity in A549 non-small-cell lung cancer cells with an IC 50 of 68 � 3 nM after 48 h of exposure. Compared to the antineoplastic agent doxorubicin, acovenoside A was more potent in inhibiting the viability of A549 cancer cells. Moreover, acovenoside A exhibited selectivity against cancer cells, being significantly less toxic to lung fibroblasts and nontoxic for peripheral blood mononuclear cells. Analysis of the cell cycle profile in acovenoside A-treated A549 cells revealed mitotic arrest, due to accumulation of the G 2 /M regulators cyclin B 1 and CDK1, and cytokinesis failure. Furthermore, acovenoside A affected the mitochondrial membrane integrity and induced production of radical oxygen species, which resulted in induction of canonical apoptosis, manifested by caspase 3 activation and DNA fragmentation. Based on our results, acovenoside A warrants further exploration as a potential anticancer lead. � 2017 The American Chemical Society and American Society of Pharmacognosy.
Ethosomes and lipid-coated chitosan nanocarriers for skin delivery of a chlorophyll derivative: A potential treatment of squamous cell carcinoma by photodynamic therapy
(Elsevier B.V., 2019) Nasr S.; Rady M.; Gomaa I.; Syrovet T.; Simmet T.; Fayad W.; Abdel-Kader M.; Institute of Pharmacology of Natural Products & Clinical Pharmacology; Ulm University; Ulm; D-89081; Germany; Department of Chemistry; School of Sciences and Engineering; American University in Cairo (AUC); Egypt; Pharmaceutical Technology Department; Faculty of Pharmacy and Biotechnology; German University in Cairo (GUC). Main Entrance of Al-Tagamoa Al-Khames New Cairo City; Egypt; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA); Egypt; Drug Bioassay-Cell Culture Laboratory; Pharmacognosy Department; National Research Centre; Dokki; Giza; 12622; Egypt; National Institute of Laser Enhanced Sciences (NILES); Cairo University (CU); Giza; Egypt
Photodynamic therapy (PDT) is a localized treatment strategy used for skin cancers such as squamous cell carcinoma (SCC), the second most common form of skin cancer. PDT combines a photosensitizer, laser source and tissue oxygen. In this study, the selected photosensitizer, ferrous chlorophyllin (Fe-CHL) was loaded in ethosomes and lipid coated chitosan (PC/CHI) nanocarriers to enhance skin delivery of Fe-CHL for potential PDT of squamous carcinoma. The nanocarrier formulations were characterized and studied for their skin retention and penetration depth of Fe-CHL across mouse skin ex vivo using high performance liquid chromatography and confocal microscopy. Confocal microscope images of mouse skin showed deeper penetration of ethosomes down to the dermis when compared to PC/CHI that was confined to the epidermis, although they showed no significant difference in skin retention. Immunohistochemistry (IHC) staining with HE, ki67 and TUNEL show maintained skin structure and no cytotoxic effects of the nanocarrier gel formulations before laser exposure to mouse skin. The nanocarriers were also studied for their PDT effect against human SCC monolayer and three-dimensional (3-D) spheroids. When compared to ethosomes, PC/CHI showed higher cytotoxicity in MTT assay and live confocal microscopy showed cell disintegration after laser exposure. For 3-D spheroids, PC/CHI also showed higher cytotoxicity using acid phosphatase assay and a decrease in spheroid size was observed using light microscopy. In conclusion, both types of nanocarriers can be used for their potential treatment of SCC using PDT depending on the tumour localization in the skin. � 2019 Elsevier B.V.