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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.)

In the course of searching for bioactive compounds from Croton species from Venezuela, two seco-entkaurenes isolated from flowers of Croton caracasana were evaluated in vitro for their effect on cell viability by the standard MTT assay in nine human cancer cell lines of different origins and one primary culture. Both compounds induced cytotoxicity in the range of 2 to 25 microM for caracasine and 0.8 to 12 microM for caracasine acid. However, for the normal fibroblasts and the cell lines, HeLa, MCF-7, PC-3, LoVo, X-17, Jurkat E6.1 and Jurkat JCaM1.6, the IC50 values of caracasine acid were lower than their counterparts. Interestingly, no differences in IC50 were recorded for the leukemic cell lines U937 and K562. It can be concluded that the acid moiety in the structure enhances the cytotoxic effect of caracasine by a pathway which seems not to be activated in the leukemic cell lines tested.

The Palauan sponge Axinyssa aplysimoides contained (3S*,5R*,6R*,9R*)-3-isocyano-1(10)-cadinene[2],(3S*,5R*,6R*, 9R*)-3-formamido-1(10)-cadinene[3], and (E)-(4-hydroxystyryl)trimethylammonium chloride [6], together with the known diterpenes (-)-neoverrucosan-5beta-ol[4] and (+)-homoverrucosan-5beta-ol[5].