Cytotoxic Effects of Artemisia annua L. and Pure Artemisinin on the D-17 Canine Osteosarcoma Cell Line

Abstract

Artemisia annua has been used for centuries in Traditional Chinese Medicine. Although used as an antimalarial drug, its active compound artemisinin and the semisynthetic derivatives have also been investigated for their anticancer properties, with interesting and promising results. The aims of this research were to evaluate (i) the cytotoxicity and the antiproliferative effect of pure artemisinin and a hydroalcoholic extract obtained from A. annua on the D-17 canine osteosarcoma cell line and (ii) the intracellular iron concentration and its correlation with the cytotoxic effects. Both artemisinin and hydroalcoholic extract induced a cytotoxic effect in a dose-dependent manner. Pure artemisinin caused an increase of cells in the S phase, whereas the hydroalcoholic extract induced an evident increase in the G2/M phase. A significant decrease of iron concentration was measured in D-17 cells treated with pure artemisinin and hydroalcoholic extract compared to untreated cells. In conclusion, although preliminary, the data obtained in this study are indicative of a more potent cytotoxic activity of the hydroalcoholic extract than pure artemisinin, indicating a possible synergistic effect of the phytocomplex and a mechanism of action involving iron and possibly ferroptosis. Considering the similarities between human and canine osteosarcomas, progress in deepening knowledge and improving therapeutic protocols will probably be relevant for both species, in a model of reciprocal translational medicine.

Medicinal Plants Used in Traditional Management of Cancer in Uganda: A Review of Ethnobotanical Surveys, Phytochemistry, and Anticancer Studies

“…e extracts inhibited cancer cell proliferation, decreased tumor growth, and induced apoptosis in vivo in triple negative breast cancer (MDA-MB-231) xenografts grown on the chick chorioallantoic membrane (CAM) assay as well as in nude mice [91]. Hydroalcoholic extract had a cytotoxic effect in a dosedependent manner against D-17 canine osteosarcoma cell lines better than pure artemisinin, indicating a possible synergistic effect of the phytocomplex and a mechanism of action involving iron and possibly ferroptosis [92] Beta vulgaris L.…”

Targeting ferroptosis in osteosarcoma

“…In the study by Hosoya et al, ROS production was detected in D17 canine OS cell lines treated with dihydroartemisinin and increased in a dose-dependent manner [78] . However, Isani et al discovered that artemisinin-intervened OS cells had reduced iron concentrations compared to untreated ones, which might contribute to the stimulation of the labile redox-active iron pool thereby promoting ROS deposition and ferroptosis [79] . The cytotoxicity of artemisinin on OS is thought to be possibly related to ferroptosis, but more robust evidence is needed to verify this.…”

A Review of Cytotoxic Plants of the Indian Subcontinent and a Broad-Spectrum Analysis of Their Bioactive Compounds

“…Dihydroartemisinin (Figure 4), a derivative of the compound was evaluated against canine OSA (Osteosarcoma) cell lines, D-17, OSCA2, OSCA16, and OSCA50 and the respective IC 50 values were 8.7, 43.6, 16.8 and 14.8 µM [38]. Apart from this, other bioactive compounds of A. annua were also tested by evaluating the cytotoxicity of its hydro-alcoholic, dichloromethane, and methanol extracts against D-17, HeLa, and TC221 cell lines, and a dose-dependent anticancer activity was observed [39,40]. For Bidens pilosa, different fractions of whole plant were evaluated, using the MTT and Comet assays, against HeLa and KB cell lines.…”