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Dehidroartemisina tópica pode ser útil no tratamento do papiloma vírus e
no câncer cervical.
06/05/10
A dehidroartemisina é droga usada no tratamento da malária.
Dihydroartemisinin is cytotoxic to papillomavirus-expressing epithelial cells in vitro and in vivo.
Disbrow GL, Baege AC, Kierpiec KA, Yuan H, Centeno JA, Thibodeaux CA, Hartmann D, Schlegel R. Cancer Res. 2005 Dec
1;65(23):10854-61.
Department of Pathology, Georgetown University Medical Center, Washington, District of Columbia 20057, USA.
Nearly all cervical cancers are etiologically attributable to human papillomavirus (HPV) infection and pharmaceutical
treatments targeting HPV-infected cells would be of great medical benefit. Because many neoplastic cells (including cervical cancer cells)
overexpress the transferrin receptor to increase their iron uptake, we hypothesized that iron-dependent, antimalarial drugs such as
artemisinin might prove useful in treating HPV-infected or transformed cells. We tested three different artemisinin compounds and found
that dihydroartemisinin (DHA) and artesunate displayed strong cytotoxic effects on HPV-immortalized and transformed cervical cells in
vitro with little effect on normal cervical epithelial cells. DHA-induced cell death involved activation of the mitochondrial caspase pathway
with resultant apoptosis. Apoptosis was p53 independent and was not the consequence of drug-induced reductions in viral oncogene
expression. Due to its selective cytotoxicity, hydrophobicity, and known ability to penetrate epithelial surfaces, we postulated that DHA
might be useful for the topical treatment of mucosal papillomavirus lesions. To test this hypothesis, we applied DHA to the oral mucosa
of dogs that had been challenged with the canine oral papillomavirus. Although applied only intermittently, DHA strongly inhibited
viral-induced tumor formation. Interestingly, the DHA-treated, tumor-negative dogs developed antibodies against the viral L1 capsid
protein, suggesting that DHA had inhibited tumor growth but not early rounds of papillomavirus replication. These findings indicate that
DHA and other artemisinin derivatives may be useful for the topical treatment of epithelial papillomavirus lesions, including those that
have progressed to the neoplastic state.
PMID: 16322232
6/10/2011 16:25