Artesunate inhibits the growth of gastric cancer cells through the mechanism of promoting oncosis both in vitro and in vivo

Abstract

This study aims to investigate the significance and mechanism of artesunate involved in suppressing the proliferation of gastric cancer in vitro and in vivo. In the in-vitro experiments, artesunate inhibited the growth of gastric cancer cell lines (SGC-7901, BGC-823, and AGS) with concentration-dependent activity, with no significant effect on GES-1 cells. BGC-823 cells treated with artesunate showed the typical morphologic features of oncosis rather than apoptosis. Meanwhile, we observed calcium overload, downregulation of vascular endothelial growth factor expression, and upregulation of calpain-2 expression in the artesunate-treated BGC-823 cells. In addition, the in-vivo study showed that artesunate produced a dose-dependent tumor regression in nude mice. The antitumor activity of 240 mg/kg artesunate was similar to that of 10 mg/kg docetaxel. Furthermore, compared with the control group, no significant difference was observed in the body weight of artesunate-treated nude mice other than docetaxel-treated nude mice. These observations show that artesunate has concentration-dependent inhibitory activities against gastric cancer in vitro and in vivo by promoting cell oncosis through an impact of calcium, vascular endothelial growth factor, and calpain-2 expression.

Nanoparticle Delivery of Artesunate Enhances the Anti-tumor Efficiency by Activating Mitochondria-Mediated Cell Apoptosis

“…Researchers also found that artemisinin and its derivatives demonstrated significant anti-tumor activity in virtue of their few toxic side effects and greater tolerance by patients [1]. It was reported that artesunate (Ats) definitely inhibited tumor cell growth and it further induced significant anti-cancer effects in tumor cells [2–4]. Some experiments indicated that Ats caused different degrees of apoptosis and oncosis in tumor cells after 48 h, and that the degrees of apoptosis and oncosis were dependent on the dose of Ats.…”

Programmed Release of Dihydroartemisinin for Synergistic Cancer Therapy Using a CaCO3 Mineralized Metal–Organic Framework

“…[9] Since the environment within tumor tissues is acidic and CaCO 3 can decompose in acidic environment, CaCO 3 has proven to be an appealing candidate for controlled drug release in tumor sites. [11] Therefore,w ei nfer that the introduction of exogenous Ca 2+ can improve oncosis efficiency and further improve the therapeutic effect of DHA. One reliable mechanism of the anticancer effect of DHA is that DHA influences the cell membrane as well the Ca 2+ pump ATPase,a nd leads to an increase in the cytosolicC a 2+ level, which activates calpains, especially calpain-2, to induce oncosis-like cell death.…”

Dehydroabietic Acid Derivative QC2 Induces Oncosis in Hepatocellular Carcinoma Cells

“…Artesunate was also a native compound which could induce oncosis in cancer cells. Zhou et al [28] found that the increase of calpain-2 level was accompanied with the oncosis event induced by artesunate and they partly elucidated the mechanisms based on calpain-2 activation. The underlying mechanism of oncosis might be related to activation of calpain.…”