Retrospective study of small pet tumors treated with Artemisia annua and iron.

Abstract

Artemisinin from Artemisia annua L. and its derivatives are well&#x2011;known antimalarial drugs. In addition, in&#xa0;vitro studies, in&#xa0;vivo studies and clinical trials have demonstrated that these drugs exhibit anticancer activity in human patients with cancer. Therefore, the aim of the present study was to investigate whether a phytotherapeutic A.&#xa0;annua preparation exerts anticancer activity in veterinary tumors of small pets. Dogs and cats with spontaneous cancer (n=20) were treated with standard therapy plus a commercial A.&#xa0;annua preparation (Luparte&#xae;) and compared with a control group treated with standard therapy alone (n=11). Immunohistochemical analyses were performed with formalin&#x2011;fixed paraffin&#x2011;embedded tumor biopsies to analyze the expression of transferrin receptor&#xa0;(TfR) and the proliferation marker Ki&#x2011;67 as possible biomarkers to assess treatment response of tumors to A.&#xa0;annua. Finally, the expression levels of TfR and Ki&#x2011;67 were compared with the IC50 values towards artemisinin in two dog tumor cells lines (DH82 and DGBM) and a panel of 54&#xa0;human tumor cell lines. Retrospectively, the present study assessed the survival times of small animals treated by standard therapy with or without A.&#xa0;annua. A.&#xa0;annua treatment was associated with a significantly higher number of animals surviving >18&#xa0;months compared with animals without A.&#xa0;annua treatment (P=0.0331). Using a second set of small pet tumors, a significant correlation was identified between TfR and Ki&#x2011;67 expression by immunohistochemistry (P=0.025). To further assess the association of transferrin and Ki&#x2011;67 expression with cellular response to artemisinin, the present study compared the expression of these two biomarkers and the IC50 values for artemisinin in National Cancer Institute tumor cell lines in&#xa0;vitro. Both markers were inversely associated with artemisinin response (P<0.05), and the expression levels of TfR and Ki&#x2011;67 were significantly correlated (P=0.008). In conclusion, the promising results of the present retrospective study warrant further confirmation by prospective studies in the future.