Dihydroartemisinin, an antimalarial drug, induces absent in melanoma 2 inflammasome activation and autophagy in human hepatocellular carcinoma HepG2215 cells

Abstract

As an effective antimalarial drug, Dihydroartemisinin (DHA) is readily isolated from the traditional Chinese medicine of Artemisia annua. DHA is not only an autophagy promoter but also a substance with strong antitumor efficiency. The relationship between autophagy and inflammasomes has been suggested in hepatocellular carcinoma (HCC). However, there are few reports describing relationships between inflammasomes and autophagy in HCC therapy. The present study demonstrated that DHA suppressed cell proliferation in HepG2215 cells in a dose‐ and time‐dependent manner. The inhibitory activity is mediated by autophagy, in which reactive oxygen species (ROS) production induced nuclear and mitochondrial DNA damage. Then, DHA were first shown to promote AIM2/caspase‐1 inflammasome. Compared with the DHA group, the autophagy inhibitor 3‐MA significantly inhibited the expressions of activated Caspase‐1, a pyroptotic marker proteins. Meanwhile, repression of mTOR by rapamycin promoted autophagy and AIM2/caspase‐1 activation. The caspase‐1 inhibitor Z‐YVAD‐FMK also notably blocked autophagy cell death characterized by the downexpression of Beclin‐1 and LC3‐II. Additionally, the study demonstrated that DHA suppressed pseudopodium formation and cell mobility. Therefore, we first reveal a novel mechanism that DHA promotes AIM2/caspase‐1 inflammasome, which contributes to autophagy in HepG2215 cells. Moreover, nuclear and mitochondrial DNA damage was also involved in this process via ROS production.

RalB degradation by dihydroartemisinin induces autophagy and IFI16/caspase-1 inflammasome depression in the human laryngeal squamous cell carcinoma

“…Our previous studies have confirmed that DHA leads to autophagy and the death of human tongue squamous cell carcinoma (TSCC) cells in vitro and in vivo [18]. Recently, our group showed that DHA induces the activation of AIM2 inflammasome in HepG2215 cells of human hepatocellular carcinoma and autophagy in HeLa cells [19,20]. DHA has selective toxicity to tumor cells and is likely to become an anticancer drug with low toxicity, high efficiency and low cost [21,22].…”

RalB degradation by dihydroartemisinin induces autophagy and IFI16/caspase-1 inflammasome depression in the human Laryngeal squamous cell carcinoma

“…For example, the suppression of IL-1β secretion by inhibiting in ammasome is expected to become a new treatment strategy in melanoma [20]. In addition, assembled in ammasomes can activate caspase-1 and cause IL-1β to be secreted from cancer cells [21]. In the present study, it was rst found that in Hep-2 cancer cells, caspase-1 was involved in the processing and secretion of IL-1β by DDP treatment in vivo.…”

RalB degradation by dihydroartemisinin induces autophagy and IFI16/caspase-1 inflammasome depression in the human Laryngeal squamous cell carcinoma

“…Our previous studies have confirmed that DHA lead to autophagy and the death of human tongue squamous cell carcinoma (TSCC) cells in vitro and in vivo [19]. Recently, our group showed that DHA induces activation of AIM2 inflammasome in HepG2215 cells of human hepatocellular carcinoma and autophagy in HeLa cells [20,21]. DHA has selective toxicity to tumor cells and is likely to become an anticancer drug with low toxicity, high efficiency and low cost [22,23].…”