Homospisulosine induced apoptosis in cervical carcinoma cells is associated with phosphorylation of Bcl-2 and up-regulation of p27/Kip1.

Autor: Pilatova MB; Pavol Jozef Safarik University, Faculty of Medicine, Department of Pharmacology, Kosice, Slovak Republic., Nosalova N; Pavol Jozef Safarik University, Faculty of Medicine, Department of Pharmacology, Kosice, Slovak Republic., Ockajakova G; Pavol Jozef Safarik University, Faculty of Medicine, Department of Pharmacology, Kosice, Slovak Republic., Kello M; Pavol Jozef Safarik University, Faculty of Medicine, Department of Pharmacology, Kosice, Slovak Republic., Kotorova K; Pavol Jozef Safarik University, Faculty of Medicine, Department of Pharmacology, Kosice, Slovak Republic., Takac P; University of Veterinary Medicine and Pharmacy, Department of Pharmacology and Toxicology, Kosice, Slovak Republic., Petik P; Pavol Jozef Safarik University, Faculty of Medicine, Department of Pathology, Kosice, Slovak Republic., Bohus P; Pavol Jozef Safarik University, Faculty of Medicine, Department of Pathology, Kosice, Slovak Republic., Stankova K; Pavol Jozef Safarik University, Faculty of Science, Department of Organic Chemistry, Institute of Chemical Sciences, Kosice, Slovak Republic., Martinkova M; Pavol Jozef Safarik University, Faculty of Science, Department of Organic Chemistry, Institute of Chemical Sciences, Kosice, Slovak Republic., Mezencev R; Georgia Institute of Technology, School of Biological Sciences, Atlanta, GA, USA.
Jazyk: angličtina
Zdroj: Journal of applied biomedicine [J Appl Biomed] 2023 Dec; Vol. 21 (4), pp. 218-227. Date of Electronic Publication: 2023 Nov 28.
DOI: 10.32725/jab.2023.019
Abstrakt: Spisulosine (1-deoxysphinganine) is a sphingoid amino alcohol isolated from the sea clams that showed potent antiproliferative activity against a broad spectrum of solid tumors but failed in clinical trials due to neurotoxicity. However, its structural similarity to other bioactive sphingoids, interesting mode of action, and appreciable potency against cancer cells make it a suitable lead for future anticancer drug development. The present study was conducted to elucidate mechanisms of the antiproliferative/cytotoxic effects of newly synthesized spisulosine analog homospisulosine (KP7). The evaluation was performed on cervical carcinoma cells, representing an in vitro model of one of the most common cancer types and a significant worldwide cause of women's cancer mortality. Treatment with homospisulosine (2.0 μM) for 24, 48, and 72 h significantly inhibited the growth of HeLa cells in vitro and induced apoptosis detectable by DNA fragmentation, externalization of phosphatidylserine, dissipation of mitochondrial membrane potential, activation of caspase-3 and cleavage of PARP. In addition, treating HeLa cells with spisulosine increased p27 and Bcl-2 on protein levels and phosphorylation of Bcl-2 on Ser70 residue. These results support the potential for spisulosine analogs represented here by homospisulosine for future therapeutic development.
Competing Interests: The authors report no conflicts of interest in this work.
Databáze: MEDLINE
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