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

Author(s):

Gricelis Patricia Martínez*, Michael Rodney Mijares, Katiuska Chávez, Perla Chirinos, Alírica Isabel Suárez, Reinaldo Santi Compagnone and Juan Bautista De Sanctis   Pages 1145 - 1155 ( 11 )

Abstract:

<p> Background: Kaurane-type diterpenoids, obtained from various natural sources, have shown many biological activities, including anti-inflammatory and antitumor effects. Caracasine, an <i>ent</i>-kaurane diterpenoid isolated from the flowers of <i>Croton micans</i>, was shown to induce apoptosis in leukaemia cell lines. </p><p> 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). </p><p> 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). </p><p> 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 (<i>p</i><0.01 in Jurkat and <i>p</i><0.05 in HL60) and caspase-8 activation (<i>p</i><0.001 in Jurkat and p<0.05 in HL60). Caspase-9 was activated in both cell lines (<i>p</i><0.001) along with the decline in mitochondrial &#916;&#968;m (<i>p</i><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-&#954;B pathway in cells pretreated with PHA to activate the NF-&#954;B pathway, suggesting a possible role in inflammatory diseases. </p><p> 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.</p>

Keywords:

Caracasine, caracasine acid, apoptosis, differentiation, caspases, NF-&#954;B, cell cycle, kaurane-type diterpenoids.

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