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2. Naturally-derived phenethyl isothiocyanate modulates apoptotic induction through regulation of the intrinsic cascade and resulting apoptosome formation in human malignant melanoma cells.

Author

Tragkola, Venetia, Anestopoulos, Ioannis, Kyriakou, Sotiris, Amery, Tom, Franco, Rodrigo, Pappa, Aglaia, and Panayiotidis, Mihalis I.

Subjects
MELANOMA, WESTERN immunoblotting, SQUAMOUS cell carcinoma, CANCER cells, SKIN cancer, PHYTOCHEMICALS
Abstract

Malignant melanoma is the most aggressive type of skin cancer with increasing incidence rates worldwide. On the other hand, watercress is a rich source of phenethyl isothiocyanate (PEITC), among others, which has been widely investigated for its anticancer properties against various cancers. In the present study, we evaluated the role of a watercress extract in modulating apoptotic induction in an in vitro model of human malignant melanoma consisting of melanoma (A375, COLO-679, COLO-800), non-melanoma epidermoid carcinoma (A431) and immortalized, non-tumorigenic keratinocyte (HaCaT) cells. Moreover, the chemical composition of the watercress extract was characterized through UPLC MS/MS and other analytical methodologies. In addition, cytotoxicity was assessed by the alamar blue assay whereas apoptosis was determined, initially, by a multiplex activity assay kit (measuring levels of activated caspases −3, −8 and −9) as well as by qRT-PCR for the identification of major genes regulating apoptosis. In addition, protein expression levels were evaluated by western immunoblotting. Our data indicate that the extract contains various phytochemicals (e.g. phenolics, flavonoids, pigments, etc.) while isothiocyanates (ITCs; especially PEITC) were the most abundant. In addition, the extract was shown to exert a significant time- and dose-dependent cytotoxicity against all malignant melanoma cell lines while non-melanoma and non-tumorigenic cells exhibited significant resistance. Finally, expression profiling revealed a number of genes (and corresponding proteins) being implicated in regulating apoptotic induction through activation of the intrinsic apoptotic cascade. Overall, our data indicate the potential of PEITC as a promising anti-cancer agent in the clinical management of human malignant melanoma. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Exploring the Role and Pathophysiological Significance of Aldehyde Dehydrogenase 1B1 (ALDH1B1) in Human Lung Adenocarcinoma.

Author

Tsochantaridis, Ilias, Brisimis, Dimitris, Tsifintaris, Margaritis, Anastasiadou, Anastasia, Lazos, Efthymios, Ermogenous, Antreas, Christou, Sylia, Antonopoulou, Nefeli, Panayiotidis, Mihalis I., Koukourakis, Michail I., Giatromanolaki, Alexandra, and Pappa, Aglaia

Subjects
DNA repair, GREEN fluorescent protein, ALDEHYDE dehydrogenase, CANCER stem cells, CELL morphology
Abstract

Aldehyde dehydrogenases (ALDHs) constitute a diverse superfamily of NAD(P)+-dependent enzymes pivotal in oxidizing endogenous and exogenous aldehydes to carboxylic acids. Beyond metabolic roles, ALDHs participate in essential biological processes, including differentiation, embryogenesis and the DNA damage response, while also serving as markers for cancer stem cells (CSCs). Aldehyde dehydrogenase 1B1 (ALDH1B1) is a mitochondrial enzyme involved in the detoxification of lipid peroxidation by-products and metabolism of various aldehyde substrates. This study examines the potential role of ALDH1B1 in human lung adenocarcinoma and its association with the CSC phenotype. To this end, we utilized the lung adenocarcinoma cell line A549, engineered to stably express the human ALDH1B1 protein tagged with green fluorescent protein (GFP). Overexpression of ALDH1B1 led to notable changes in cell morphology, proliferation rate and clonogenic efficiency. Furthermore, ALDH1B1-overexpressing A549 cells exhibited enhanced resistance to the chemotherapeutic agents etoposide and cisplatin. Additionally, ALDH1B1 overexpression correlated with increased migratory potential and epithelial–mesenchymal transition (EMT), mediated by the upregulation of transcription factors such as SNAI2, ZEB2 and TWIST1, alongside the downregulation of E-cadherin. Moreover, Spearman's rank correlation coefficient analysis using data from 507 publicly available lung adenocarcinoma clinical samples revealed a significant correlation between ALDH1B1 and various molecules implicated in CSC-related signaling pathways, including Wnt, Notch, hypoxia, Hedgehog, retinoic acid, Hippo, NF-κΒ, TGF-β, PI3K/PTEN-AKT and glycolysis/gluconeogenesis. These findings provide insights into the role of ALDH1B1 in lung tumor progression and its relation to the lung CSC phenotype, thereby offering potential therapeutic targets in the clinical management of lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Investigation of Potential Gut Health Biomarkers in Broiler Chicks Challenged by Campylobacter jejuni and Submitted to a Continuous Water Disinfection Program

Author

Mantzios, Tilemachos, primary, Kiousi, Despoina E., additional, Brellou, Georgia D., additional, Papadopoulos, Georgios A., additional, Economou, Vangelis, additional, Vasilogianni, Marili, additional, Kanari, Elisavet, additional, Petridou, Evanthia, additional, Giannenas, Ilias, additional, Tellez-Isaias, Guillermo, additional, Pappa, Aglaia, additional, Galanis, Alex, additional, and Tsiouris, Vasilios, additional

Published
2024
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8. Isothiocyanates Potentiate Tazemetostat-Induced Apoptosis by Modulating the Expression of Apoptotic Genes, Members of Polycomb Repressive Complex 2, and Levels of Tri-Methylating Lysine 27 at Histone 3 in Human Malignant Melanoma Cells

Author

Anestopoulos, Ioannis, primary, Paraskevaidis, Ioannis, additional, Kyriakou, Sotiris, additional, Giova, Lambrini E., additional, Trafalis, Dimitrios T., additional, Botaitis, Sotiris, additional, Franco, Rodrigo, additional, Pappa, Aglaia, additional, and Panayiotidis, Mihalis I., additional

Published
2024
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10. Revisiting Temozolomide's role in solid tumors: Old is gold?

Author

Matthaios, Dimitrios, primary, Balgkouranidou, Ioanna, additional, Neanidis, Konstantinos, additional, Sofis, Andreas, additional, Pikouli, Anastasia, additional, Romanidis, Konstantinos, additional, Pappa, Aglaia, additional, Karamouzis, Michael, additional, Zygogianni, Anna, additional, Charalampidis, Charalampos, additional, Zarogoulidis, Paul, additional, Rigas, George, additional, and Galanis, Alex, additional

Published
2024
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15. A Naturally Derived Watercress Flower-Based Phenethyl Isothiocyanate-Enriched Extract Induces the Activation of Intrinsic Apoptosis via Subcellular Ultrastructural and Ca2+ Efflux Alterations in an In Vitro Model of Human Malignant Melanoma

Author

Kyriakou, Sotiris, primary, Potamiti, Louiza, additional, Demosthenous, Nikoletta, additional, Amery, Tom, additional, Stewart, Kyle, additional, Winyard, Paul G., additional, Franco, Rodrigo, additional, Pappa, Aglaia, additional, and Panayiotidis, Mihalis I., additional

Published
2023
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23. A Naturally Derived Watercress Flower-Based Phenethyl Isothiocyanate-Enriched Extract Induces the Activation of Intrinsic Apoptosis via Subcellular Ultrastructural and Ca 2+ Efflux Alterations in an In Vitro Model of Human Malignant Melanoma.

Author

Kyriakou, Sotiris, Potamiti, Louiza, Demosthenous, Nikoletta, Amery, Tom, Stewart, Kyle, Winyard, Paul G., Franco, Rodrigo, Pappa, Aglaia, and Panayiotidis, Mihalis I.

Abstract

The aim of the current study was to (i) extract isolated fractions of watercress flowers enriched in polyphenols, phenethyl isothiocyanate and glucosinolates and (ii) characterize the anticancer mode of action of non-lethal, sub-lethal and lethal concentrations of the most potent extract fraction in primary (A375) and metastatic (COLO-679) melanoma cells as well as non-tumorigenic immortalized keratinocyte (HaCaT) cells. Cytotoxicity was assessed via the Alamar Blue assay, whereas ultrastructural alterations in mitochondria and the endoplasmic reticulum were determined via transmission electron microscopy. Mitochondrial membrane depolarization was determined using Mito-MP dye, whereas apoptosis was evaluated through the activation of caspases-3, -8 and -9. Among all extract fractions, the phenethyl isothiocyanate-enriched one (PhEF) possessed significant cytotoxicity against A375 and COLO-679 cells, while HaCaT cells remained relatively resistant at sub-lethal and lethal concentrations. Additionally, ultrastructural subcellular alterations associated with apoptosis were observed by means of increased mitochondrial area and perimeter, decreased cristae density and a shorter distance of the endoplasmic reticulum to the mitochondria, all taking place during "early" time points (2–4 h) of exposure. Moreover, PhEF induced mitochondrial membrane depolarization associated with "late" time points (24 h) of exposure, thereby leading to the activation of intrinsic apoptosis. Finally, the inhibition of cytosolic Ca2+ efflux reduced levels of caspases-9 and -3 activity, suggesting the involvement of Ca2+ efflux in modulating the activation of intrinsic apoptosis. To conclude, our data demonstrate an association of "early" ultrastructural alterations in mitochondria and the endoplasmic reticulum with the "late" induction of intrinsic apoptosis via the modulation of Ca2+ efflux. [ABSTRACT FROM AUTHOR]

Published
2023
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27. Chemical Profiling, Antiproliferative and Antimigratory Capacity of Haberlea rhodopensis Extracts in an In Vitro Platform of Various Human Cancer Cell Lines

Author

Spyridopoulou, Katerina, primary, Kyriakou, Sotiris, additional, Nomikou, Angeliki, additional, Roupas, Angelos, additional, Ermogenous, Antreas, additional, Karamanoli, Katerina, additional, Moyankova, Daniela, additional, Djilianov, Dimitar, additional, Galanis, Alex, additional, Panayiotidis, Mihalis I., additional, and Pappa, Aglaia, additional

Published
2022
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29. Multi-method biophysical analysis in discovery, identification, and in-depth characterization of surface‐active compounds

Author

Zompra, Aikaterini A., primary, Chasapi, Styliani A., additional, Twigg, Matthew S., additional, Salek, Karina, additional, Anestopoulos, Ioannis, additional, Galanis, Alex, additional, Pappa, Aglaia, additional, Gutierrez, Tony, additional, Banat, Ibrahim M., additional, Marchant, Roger, additional, Euston, Stephen R., additional, Panayiotidis, Mihalis I., additional, and Spyroulias, Georgios A., additional

Published
2022
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36. Evaluation of Bioactive Properties of Lipophilic Fractions of Edible and Non-Edible Parts of Nasturtium officinale (Watercress) in a Model of Human Malignant Melanoma Cells

Author

Kyriakou, Sotiris, primary, Tragkola, Venetia, additional, Alghol, Heba, additional, Anestopoulos, Ioannis, additional, Amery, Tom, additional, Stewart, Kyle, additional, Winyard, Paul G., additional, Trafalis, Dimitrios T., additional, Franco, Rodrigo, additional, Pappa, Aglaia, additional, and Panayiotidis, Mihalis I., additional

Published
2022
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37. Targeting the Epigenome in Malignant Melanoma: Facts, Challenges and Therapeutic Promises

Author

Anestopoulos, Ioannis, primary, Kyriakou, Sotiris, additional, Tragkola, Venetia, additional, Paraskevaidis, Ioannis, additional, Tzika, Eleni, additional, Mitsiogianni, Melina, additional, Deligiorgi, Maria, additional, Petrakis, Giorgos, additional, Trafalis, Dimitrios T., additional, Botaitis, Sotiris, additional, Giatromanolaki, Alexandra, additional, Koukourakis, Michail I., additional, Rodrigo, Franco, additional, Pappa, Aglaia, additional, and Panagiotidis, Mihalis, additional

Published
2022
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38. Chemical and Biological Characterization of the Anticancer Potency of Salvia fruticosa in a Model of Human Malignant Melanoma

Author

Kyriakou, Sotiris, primary, Tragkola, Venetia, additional, Plioukas, Michael, additional, Anestopoulos, Ioannis, additional, Chatzopoulou, Paschalina S., additional, Sarrou, Eirini, additional, Trafalis, Dimitrios T., additional, Deligiorgi, Maria V., additional, Franco, Rodrigo, additional, Pappa, Aglaia, additional, and Panayiotidis, Mihalis I., additional

Published
2021
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44. Protective role of taurine against oxidative stress (Review)

Author

Baliou, Stella, primary, Adamaki, Maria, additional, Ioannou, Petros, additional, Pappa, Aglaia, additional, Panayiotidis, Mihalis, additional, Spandidos, Demetrios, additional, Christodoulou, Ioannis, additional, Kyriakopoulos, Anthony, additional, and Zoumpourlis, Vassilis, additional

Published
2021
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45. Chemical and Biological Characterization of the Anticancer Potency of Salvia fruticosa in a Model of Human Malignant Melanoma

Author

Kyriakou, Sotiris Tragkola, Venetia Plioukas, Michael and Anestopoulos, Ioannis Chatzopoulou, Paschalina S. Sarrou, Eirini and Trafalis, Dimitrios T. Deligiorgi, Maria V. Franco, Rodrigo and Pappa, Aglaia Panayiotidis, Mihalis I.

Abstract

Malignant melanoma is one of the most aggressive types of skin cancer with an increasing incidence worldwide. Thus, the development of innovative therapeutic approaches is of great importance. Salvia fruticosa (SF) is known for its anticancer properties and in this context, we aimed to investigate its potential anti-melanoma activity in an in vitro model of human malignant melanoma. Cytotoxicity was assessed through a colorimetric-based sulforhodamine-B (SRB) assay in primary malignant melanoma (A375), non-malignant melanoma epidermoid carcinoma (A431) and non-tumorigenic melanocyte neighbouring keratinocyte (HaCaT) cells. Among eight (8) different fractions of S. fruticosa extracts (SF1-SF8) tested, SF3 was found to possess significant cytotoxic activity against A375 cells, while A431 and HaCaT cells remained relatively resistant or exerted no cytotoxicity, respectively. In addition, the total phenolic (Folin-Ciocalteu assay) and total flavonoid content of SF extracts was estimated, whereas the antioxidant capacity was measured via the inhibition of tert-butyl hydroperoxide-induced lipid peroxidation and protein oxidation levels. Finally, apoptotic cell death was assessed by utilizing a commercially available kit for the activation of caspases - 3, - 8 and - 9. In conclusion, the anti-melanoma properties of SF3 involve the induction of both extrinsic and intrinsic apoptotic pathway(s), as evidenced by the increased activity levels of caspases - 8, and - 9, respectively.

Published
2021

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