Artemisinin reduces human melanoma cell migration by down-regulating αVβ3 integrin and reducing metalloproteinase 2 production

Abstract

Artemisinin and its derivatives are well known antimalarial drugs, particularly useful after resistance to traditional antimalarial pharmaceuticals has started to occur in Plasmodium falciparum. In recent years, anticancer activity of artemisinin has been reported both in vitro and in vivo. Artemisinin has inhibitory effects on cancer cell growth and anti-angiogenetic activity. In the present investigation, we analyzed the inhibitory effects of artemisinin on migratory ability of melanoma cell lines (A375P and A375M, low and medium metastatic properties, respectively). We demonstrate that artemisinin induces cell growth arrest in A375M, and affects A375P cells viability with cytotoxic and growth inhibitory effects, while it was not effective in contrasting proliferation of other tumor cell lines (MCF7 and MKN). In addition, artemisinin affected the migratory ability of A375M cells by reducing metalloproteinase 2 (MMP-2) production and down-regulating alpha v beta 3 integrin expression. These findings introduce a potential of artemisinin as a chemotherapeutic agent in melanoma treatment.

Dihydroartiminisin inhibits the growth and metastasis of epithelial ovarian cancer

“…Our data show that DHA inhibits ovarian cancer via reducing the proliferation and adhesion of ovarian epithelial cancer cells in vitro. These data are consistent with other findings that DHA is able to inhibit the proliferation of several other malignant cell lines (3)(4)(5)(6)(7)(22)(23)(24)(25).…”

“…Our study demonstrated that DHA inhibit production of MMP-2 only, suggesting that DHA may differentially regulate MMPs and inhibit ovarian cancer metastasis via the MMP-2 pathway. Our data are consistent with the previous observation that inhibition of cell migration by artemisinin (an analogue of DHA) was associated with decreased expression of MMP-2 (22). On the other hand, MMP-9 is highly up-regulated in ovarian cancer, particularly in metastases (19).…”

“…Our results showed that DHA inhibited cell migration and invasion significantly in human ovarian cancer cells in a dose-dependent manner, which is in line with the findings that DHA inhibited migration of melanoma cells (22) and sarcoma cells (26). Tan et al, however, reported that DHA had no effect on human ovarian cancer cell line SKOV3 (27).…”

Ludartin treatment exhibits promising inhibitory effect on the epithelial ovarian cancer growth and metastasis

“…There are reports that inhibition of carcinoma cell adhesion using various chemotherapeutic agents plays an important role in cancer treatment (Efferth et al, 2001;Huang et al, 2007;Buommino et al, 2009). …”

In vitro study of the anti-cancer effects of artemisone alone or in combination with other chemotherapeutic agents

“…Studies have identified several potential mechanisms by which the artemisinins can act against cancer cells. They have been shown to be antiproliferative through action on key cell cycle regulatory proteins such as p21 waf1cip1 and cyclin D1 [20]; pro-apoptotic by manipulating the Bax:Bcl-2 rheostat [21,22]; antiangiogenic by targeting vascular endothelial growth factor [23,24]; and anti-migratory through their effects on αVβ3 integrins [25]. The multi-modal character of these antimalarial drugs, allied to their low host toxicity even at high doses [26,27], reinforces the priority for them to be developed as a novel anti-cancer agents.…”