Title:Caracasine, An ent-kaurane Diterpene with Proapoptotic and Pro-differentiator Activity in Human Leukaemia Cell Lines
Volume: 23
Issue: 10
Author(s): Gricelis Patricia Martínez*, Michael Rodney Mijares, Katiuska Chávez, Perla Chirinos, Alírica Isabel Suárez, Reinaldo Santi Compagnone and Juan Bautista De Sanctis
Affiliation:
- Institute of Immunology, Faculty of Medicine, Central University of Venezuela, Caracas, Venezuela.
Keywords:
Caracasine, caracasine acid, apoptosis, differentiation, caspases, NF-κB, cell cycle, kaurane-type diterpenoids.
Abstract:
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.
