In vitro and in vivo antiproliferative activity of laherradurin and cherimolin-2 of Annona diversifolia Saff.

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Phytother Res. 2009 Aug;23(8):1128-33.

In vitro and in vivo antiproliferative activity of laherradurin and cherimolin-2 of Annona diversifolia Saff.
 
Schlie-Guzmán MA, García-Carrancá A, González-Esquinca AR.
Escuela
de Biología, Universidad de Ciencias y Artes de Chiapas. Libramiento
Norte Poniente s/n, C. P. 29039, Tuxtla Gutiérrez, Chiapas, México.
Acetogenins
from Annonaceae (ACG) are potent inhibitors of the mitochondrial
complex I, they present cytotoxic activity on neoplasic lines,
including those with multiresistance to drugs. In vivo antitumor
activities of some ACG have been reported; however, no information is
available regarding the relationship between their cytotoxic activity
in cell cultures and their antiproliferative action in vivo.
Laherradurin and cherimolin-2 acetogenins were isolated from Annona
diversifolia seeds, and their inhibitory potential was analysed in
vitro on HeLa and SW-480 cells. Doses containing 1, 10, 100 and 500
times the IC50 obtained from the proliferation assays and multiplied by
the weight of the animal, were injected once daily into athymic mice
bearing these cancer cell lines; their effect upon tumor growth was
measured over a period of 20 days. Laherradurin was more active than
cherimolin-2, and it showed in in vitro proliferation assays a similar
IC50 in both neoplasic lines. In athymic mice, laherradurin
administered in 10x, 100x and 500x doses, reduced the size of HeLa
tumors, and with 100x and 500x doses, affected the SW-480 tumor
development. These doses were similar to results found with the control
drug doxorubicin (p < or = 0.05). On the other hand, cherimolin-2
had an effect on HeLa tumors cells at 100x and 500x doses (p < or =
0.05). Copyright 2009 John Wiley & Sons, Ltd.