PLoS One Dihydroartemisinin Induces Apoptosis of Liver Cancer Cells

The prevalence and mortality of liver cancer are among the top five of all cancers, and the scientific community has also been focusing on the development of new strategies for the treatment of liver cancer. Artemisinin (artemisinin) is a kind of high-efficiency and low-toxicity antimalarial drug that was firstly isolated and extracted from "Artemisia annua L." by researchers in China. Artemisinin contains a unique peroxide bridge, which can react with ferrous ions to form oxygen free radicals, induce cell damage and cell death, or damage cell structure and function through direct oxidation, leading to cell death.

Dihydroartemisinin (DHA) is the main metabolite of artemisinin drugs in vivo. Compared with artemisinin, DHA has better water-solubility and stronger antimalarial efficacy. Recent studies have shown that dihydroartemisinin (DHA) has antitumor activity against liver cancer.

In a recent study published in PLoSOne magazine, scientists demonstrated that histone deacetylase inhibitors (HDACi) significantly enhance the anti-tumor effects of DHA by increasing the apoptosis of tumor cells in vitro and in vivo. DHA-induced apoptosis is due to inhibition of ERK phosphorylation, and the combination of ERK phosphorylation inhibitor PD98059 can increase DHA-induced apoptosis.

Compared with DHA alone, combined treatment with DHA and HDACI reduced mitochondrial membrane potential, released cytochrome c into the cytoplasm, increased expression of P53 and Bak, decreased expression of Mcl-1 and p-ERK, and activated caspase3 and PARP. Also increased, these effects consistently induced tumor cell apoptosis.

In addition, studies have found that HDACI pretreatment of tumor cells is conducive to DHA-induced apoptosis. In a nude mouse model of HepG2 cells, intraperitoneal injection of DHA and SAHA significantly inhibited tumor growth. The results of TUNEL and H&E staining showed that the combination therapy inhibited cell growth because it could induce tumor cell apoptosis. Immunohistochemical data showed that PARP activation, Ki-67, p-ERK and Mcl-1 expression decreased.

In summary, the data suggest that the combined use of HDACi and DHA may be a very promising treatment strategy for liver cancer with anti-tumor effects.

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