Cancer: Breast, leukemia, gastric
Action: Anti-cancer
Artemisinin is isolated from Artemisia annua (L.).
Anti-cancer
Artemisinin and related compounds (artemisinins) is a frontline treatment for malaria. According to experimental evidence from more than 400 literature studies, 558 key proteins were derived and the artemisinins-rewired protein interaction network was constructed. Topological properties were analyzed to show that the protein network was a scale-free biological system. Five key pathways including PI3K-Akt, T cell receptor, Toll-like receptor, TGF-beta and insulin signaling pathways were involved in artemisinins-mediated anti-cancer effects (Huang et al., 2013).
Breast Cancer
Artemisinin has previously been shown to have selective toxicity towards cancer cells in vitro. The potential of artemisinin to prevent breast cancer development has been investigated in rats treated with a single oral dose (50 mg/kg) of 7,12-dimethylbenz[a]anthracene (DMBA), known to induce multiple breast tumors. Starting from the day immediately after DMBA treatment, one group of rats was provided with a powdered rat-chow containing 0.02% artemisinin, whereas a control group was provided with plain powdered food. For 40 weeks, both groups of rats were monitored for breast tumors.
Oral artemisinin significantly delayed (P<.002) and in some animals prevented (57% of artemisinin-fed versus 96% of the controls developed tumors, P<.01) breast cancer development in the monitoring period. In addition, breast tumors in artemisinin-fed rats were significantly fewer (P<.002) and smaller in size (P<.05) when compared with controls. Since artemisinin is a relatively safe compound that causes no known side-effects even at high oral doses, the present data indicate that artemisinin may be a potent chemoprevention agent (Lai, 2006).
Leukemia
Artemisinin is also a well-known anti-leukemic agent. The effect of artemisinin on cellular differentiation in the human promyelocytic leukemia HL-60 cell culture system has been investigated. Artemisinin markedly increased the degree of HL-60 leukemia cell differentiation when simultaneously combined with low doses of 1α,25-dihydoxyvitamin D3 [1,25-(OH)2D3] or all-trans retinoic acid (all-trans RA).
Extracellular-regulated kinase (ERK) inhibitors markedly inhibited HL-60 cell differentiation induced by artemisinin in combination with 1,25-(OH)2D3 or all-trans RA, whereas phosphatidylinositol 3-kinase (PI3-K) inhibitors did not. Particularly, protein kinase C (PKC) inhibitors inhibited HL-60 cell differentiation induced by artemisinin in combination with 1,25-(OH)2D3 but not with all-trans RA. Artemisinin enhanced PKC activity and protein level of PKCβI isoform in only 1,25-(OH)2D3-treated HL-60 cells.
Taken together, these results indicate that artemisinin strongly enhances the action of low doses of 1α,25-dihydoxyvitamin D3 [1,25-(OH)2D3] and all-trans retinoic acid in leukemia cell differentiation (Kim, 2003).
Gastric Cancer
Zhang et al. (2013) found that artemisinin inhibited growth and modulated expression of cell-cycle regulators in gastric cancer cells (AGS and MKN74 cells). Treatment with artemisinin was also associated with induction of p27kip1 and p21kip1, two negative cell-cycle regulators. Furthermore, we revealed that artemisinin treatment led to an increased expression of p53.
The side-effects from the artemisinin class of medications are similar to the symptoms of malaria: nausea, vomiting, anorexia, and dizziness. Mild blood abnormalities have also been noted. A rare but serious adverse effect is allergic reaction (Leonardi et al., 2001).
References
Huang C, Ba Q, Yue Q, et al. (2013). Artemisinin rewires the protein interaction network in cancer cells: network analysis, pathway identification, and target prediction. Mol Biosyst. Kim SH, Kim HJ, Kim TS. (2003). Differential involvement of protein kinase C in human promyelocytic leukemia cell differentiation enhanced by artemisinin. European Journal of Pharmacology, 482(1–3):67–76. doi:10.1016/j.ejphar.2003.09.057.