Artesunate

Artesunate is an antimalarial compound and an inhibitor of signal transducer and activator of transcription 3 (STAT-3) and membrane glutathione S-transferase (EXP1) ^{[1, 2]}. Artesunate is a sesquiterpene lactone with anti-tumor, anti-inflammatory, anti-fibrotic, and antiviral activities ^[3].

In vitro, treatment of gastric cancer cell line SGC-7901 cells with artesunate (0, 30, 60, 120 mM) for 24 h significantly increased the cell apoptosis rate, Bax and Caspase-3 protein expression levels, and significantly reduced the cell proliferation index, CDC25A, Bcl-2 protein expression, and mitochondrial membrane potential ^[4]. Treatment of human glioma cells LN-229 with artesunate (5-50 μg/mL) induced apoptosis and necrosis, DNA oxidative damage, and a continuous increase in DNA double-strand breaks, causing a dose-dependent increase in the levels of phosphorylated ATM, ATR, Chk2, and Chk1 ^[5].

In vivo, Artesunate (50 mg/kg) was intraperitoneally injected into mice transplanted with ovarian cancer cells (A2780 and HO8910 cells) for 16 days. Treatment alone had no significant effect on the growth of both transplanted tumors, while the tumor growth of the group treated with cisplatin was significantly slowed down^[6]. Artesunate (200 mg/kg) was orally treated with mice infected with Plasmodium berghei, which significantly reduced the number of congested capillaries, endothelial cell thickness, and detachment of leukocytes from the vascular wall in brain slices, and reduced the expression of TNF-α in brain tissue ^[7].

References:
[1] Ilamathi M, Santhosh S, Sivaramakrishnan V. Artesunate as an anti-cancer agent targets stat-3 and favorably suppresses hepatocellular carcinoma[J]. Current topics in medicinal chemistry, 2016, 16(22): 2453-2463.
[2] Lisewski A M, Quiros J P, Ng C L, et al. Supergenomic network compression and the discovery of EXP1 as a glutathione transferase inhibited by artesunate[J]. Cell, 2014, 158(4): 916-928.
[3] Shi M, Yang X. Research Progress on Anti-tumor Mechanism of Artesunate Combined Drugs[J]. Academic Journal of Science and Technology, 2024, 10(1): 197-201.
[4] Wang L, Liu L, Wang J, et al. Inhibitory effect of artesunate on growth and apoptosis of gastric cancer cells[J]. Archives of medical research, 2017, 48(7): 623-630.
[5] Berdelle N, Nikolova T, Quiros S, et al. Artesunate induces oxidative DNA damage, sustained DNA double-strand breaks, and the ATM/ATR damage response in cancer cells[J]. Molecular cancer therapeutics, 2011, 10(12): 2224-2233.
[6] Wang B, Hou D, Liu Q, et al. Artesunate sensitizes ovarian cancer cells to cisplatin by downregulating RAD51[J]. Cancer biology & therapy, 2015, 16(10): 1548-1556.
[7] Souza M C, Paixao F H M, Ferraris F K, et al. Artesunate Exerts a Direct Effect on Endothelial Cell Activation and NF‐κB Translocation in a Mechanism Independent of Plasmodium Killing[J]. Malaria research and treatment, 2012, 2012(1): 679090.

青蒿琥酯（Artesunate）是一种抗疟疾化合物，是信号转导及转录激活蛋白3（STAT-3）和膜谷胱甘肽S-转移酶（EXP1）的抑制剂^{[1, 2]}。Artesunate是一种倍半萜内酯，具有抗肿瘤、抗炎、抗纤维化、抗病毒等活性^[3]。

在体外，Artesunate（0, 30, 60, 120mM）处理胃癌细胞株SGC-7901细胞24h，显著升高了细胞凋亡率、Bax、Caspase-3蛋白表达水平，显著降低了细胞增殖指数、CDC25A、Bcl-2蛋白表达及线粒体膜电位^[4]。Artesunate（5-50μg/mL）处理人胶质瘤细胞LN-229，诱导了细胞凋亡和坏死、DNA氧化损伤以及DNA双链断裂持续增加，引起磷酸化ATM、ATR、Chk2和Chk1水平的剂量依赖性增加^[5]。

在体内，Artesunate（50mg/kg）通过腹腔注射治疗移植了卵巢癌细胞（A2780和HO8910细胞）的小鼠16天，单独治疗对两种移植瘤的生长无明显影响，而联合顺铂治疗组的肿瘤生长明显减缓^[6]。Artesunate（200mg/kg）通过口服治疗伯氏疟原虫感染的小鼠，显著减少了脑切片中充血的毛细血管数量、内皮细胞厚度和白细胞与血管壁的脱离，减少了脑组织中TNF- α的表达^[7]。