Caracasine, An ent -kaurane Diterpene with Proapoptotic and Pro-differentiator Activity in Human Leukaemia Cell Lines.

Autor:	Martínez GP; Institute of Immunology, Faculty of Medicine, Central University of Venezuela, Caracas, Venezuela., Mijares MR; Institute of Immunology, Faculty of Medicine, Central University of Venezuela, Caracas, Venezuela.; Biotecnology Unit, Faculty of Pharmacy, Central University of Venezuela, Caracas, Venezuela., Chávez K; Natural Products Unit, Faculty of Pharmacy, Central University of Venezuela, Caracas, Venezuela., Chirinos P; Institute of Immunology, Faculty of Medicine, Central University of Venezuela, Caracas, Venezuela., Suárez AI; Natural Products Unit, Faculty of Pharmacy, Central University of Venezuela, Caracas, Venezuela., Compagnone RS; School of Chemistry, Faculty of Sciences, Central University of Venezuela, Caracas, Venezuela., De Sanctis JB; Institute of Immunology, Faculty of Medicine, Central University of Venezuela, Caracas, Venezuela.; Czech Advanced Technology and Research Institute (CATRIN), Institute of Molecular and Translational Medicine, Palacky University, Hněvotínská 1333/5, 779 00, Olomouc, Czech Republic.
Jazyk:	angličtina
Zdroj:	Anti-cancer agents in medicinal chemistry [Anticancer Agents Med Chem] 2023; Vol. 23 (10), pp. 1145-1155.
DOI:	10.2174/1871520622666220415105615
Abstrakt:	Background: Kaurane-type diterpenoids, obtained from various natural sources, have shown many biological activities, including anti-inflammatory and antitumor effects. Caracasine, an ent -kaurane diterpenoid isolated from the flowers of Croton micans , was shown to induce apoptosis in leukaemia cell lines. Objective: The present study aimed to ascertain the compound's mechanism of cell death induction using two leukaemia cell lines, Jurkat E6.1 (T cell) and HL-60 (promyeloblast cells). Methods: Cell death in Jurkat and HL60 cells were evaluated by flow cytometry for apoptosis with annexin-V/PI, mitochondrial membrane potential disturbance, changes in cell cycle, CD95 expression, caspase activation, Nuclear Factor kappa B inhibition, and differentiation into a neutrophil-like cell (dHL60). Results: Caracasine (10 μM) increased the G0/G1 phase in Jurkat and arrested the cell cycle in the S phase in HL60. Caracasine increased CD95 expression ( p <0.01 in Jurkat and p <0.05 in HL60) and caspase-8 activation ( p <0.001 in Jurkat and p<0.05 in HL60). Caspase-9 was activated in both cell lines ( p <0.001) along with the decline in mitochondrial Δψm ( p <0.05 in Jurkat and p<0.001 in HL60). In HL60 cells, the kaurane induced neutrophil differentiation was assessed by CD40 expression and reactive oxygen species production. In Jurkat cells, caracasine inhibited the NF-κB pathway in cells pretreated with PHA to activate the NF-κB pathway, suggesting a possible role in inflammatory diseases. Conclusion: Caracasine induced apoptosis through the intrinsic and extrinsic pathways in both cell lines were evaluated which could be the leading structure for new anti-leukemic and anti-inflammatory drugs. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
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