Abstract
Artemisinin, a chemical compound used for the treatment of malaria, has been known to show anti-cancer activity. However, the effect of this chemical on natural killer (NK) cells, which are involved in tumor killing, remains unknown. Here, we demonstrate that artemisinin exerts a potent anti-cancer effect by activating NK cells. NK-92MI cells pre-treated with artemisinin were subjected to a cytotoxicity assay using K562 cells. The results showed that artemisinin significantly enhances the cytolytic activity of NK cells in a dose-dependent manner. Additionally, the artemisinin-enhanced cytotoxic effect of NK-92MI cells on tumor cells was accompanied by the stimulation of granule exocytosis, as evidenced by the detection of CD107a expression in NK cells. Moreover, this enhancement of cytotoxicity by artemisinin was also observed in human primary NK cells from peripheral blood. Our results suggest that artemisinin enhances human NK cell cytotoxicity and degranulation. This is the first evidence that artemisinin exerts antitumor activity by enhancing NK cytotoxicity. Therefore, these results provide a deeper understanding of the action of artemisinin and will contribute to the development and application of this class of compounds in cancer treatment strategies.
Highlights
Artemisinin is a chemical compound extracted from the plant of sweet wormwood (Artemisia annua L.), and is a Chinese traditional medicine that has been used in the treatment of malaria [1,2]
We found that artemisinin significantly enhances natural killer (NK) cell cytotoxic activity through granule exocytosis
These results suggest that artemisinin directly increases the cytolytic activity of NK cells
Summary
Artemisinin is a chemical compound extracted from the plant of sweet wormwood (Artemisia annua L.), and is a Chinese traditional medicine that has been used in the treatment of malaria [1,2]. Following the stimulation of activating receptors downstream signaling, lytic granules in NK cells move to the microtubule-organizing center (MTOC) along with the microtubule, and the MTOC becomes polarized toward the NK-target cell contact area [11,12]. There is a significant benefit in developing strategies to induce the exocytosis of lytic granules of NK cells for targeted cancer therapy [10]. This study investigated the function of artemisinin on the cytotoxic effects of NK cells toward cancer cells. We found that artemisinin significantly enhances NK cell cytotoxic activity through granule exocytosis. This provides the first evidence of a potent anti-cancer effect of artemisinin through upregulation of NK activity
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