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


Дәйексөз келтіру

Толық мәтін

Аннотация

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.

Авторлар туралы

Gricelis Martínez

Institute of Immunology, Faculty of Medicine, , Central University of Venezuela

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Michael Mijares

Institute of Immunology, Faculty of Medicine,, Central University of Venezuela

Email: info@benthamscience.net

Katiuska Chávez

Natural Products Unit, Faculty of Pharmacy,, Central University of Venezuela

Email: info@benthamscience.net

Perla Chirinos

nstitute of Immunology, Faculty of Medicine, Central University of Venezuela,

Email: info@benthamscience.net

Alírica Suárez

Natural Products Unit, Faculty of Pharmacy,, Central University of Venezuela,

Email: info@benthamscience.net

Reinaldo Compagnone

School of Chemistry, Faculty of Sciences,, Central University of Venezuela

Email: info@benthamscience.net

Juan De Sanctis

Institute of Immunology, Faculty of Medicine, Central University of Venezuela,

Email: info@benthamscience.net

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