Dihydroartemisinin

Dihydroartemisinin (DHA) is an active metabolite of artemisinin and its derivatives (ARTs) and is an effective drug widely used in the clinic to treat malaria^[1]. Dihydroartemisinin exerts its anticancer effects through multiple molecular mechanisms, including inhibiting proliferation, inducing apoptosis, inhibiting tumor metastasis and angiogenesis, promoting immune function, inducing autophagy and endoplasmic reticulum stress^[2]. Dihydroartemisinin can exert its cytotoxic effects through Fe(II)-mediated endoperoxide cleavage^[3].

In vitro, Dihydroartemisinin (2.5-120μM) treated esophageal cancer cells (Eca109 and Ec9706 cells) for 48 and 72h, reducing cell viability in a dose-dependent manner, with IC₅₀ values of 76.86μM and 93.81μM, respectively, and inducing cell apoptosis and cell cycle arrest^[4]. Dihydroartemisinin (0-80µM) treatment of gastric cancer cells (SGC-7901, BGC823, and MGC803 cells) for 48 and 72h reduced cell viability in a dose-dependent manner and induced cell G1 arrest, apoptosis, and senescence^[5].

In vivo, Dihydroartemisinin (20mg/kg) was intraperitoneally injected into mice inoculated with human hepatoma cells (HepG2) for 4 weeks, which significantly inhibited tumor growth and induced apoptosis of tumor tissue cells^[6]. Dihydroartemisinin (20mg/kg) was intraperitoneally injected into colon cancer mice for 30 days, which significantly inhibited colon tumor formation, induced apoptosis of tumor tissue cells, and increased the expression of peroxisome proliferator-activated receptor γ (PPARγ)^[7].

References:
[1] Zhang X G, Li G X, Zhao S S, et al. A review of dihydroartemisinin as another gift from traditional Chinese medicine not only for malaria control but also for schistosomiasis control[J]. Parasitology research, 2014, 113: 1769-1773.
[2] Dai X, Zhang X, Chen W, et al. Dihydroartemisinin: a potential natural anticancer drug[J]. International journal of biological sciences, 2021, 17(2): 603.
[3] Antoine T, Fisher N, Amewu R, et al. Rapid kill of malaria parasites by artemisinin and semi-synthetic endoperoxides involves ROS-dependent depolarization of the membrane potential[J]. Journal of antimicrobial chemotherapy, 2014, 69(4): 1005-1016.
[4] Du X X, Li Y J, Wu C L, et al. Initiation of apoptosis, cell cycle arrest and autophagy of esophageal cancer cells by dihydroartemisinin[J]. Biomedicine & Pharmacotherapy, 2013, 67(5): 417-424.
[5] Sun H, Meng X, Han J, et al. Anti-cancer activity of DHA on gastric cancer—an in vitro and in vivo study[J]. Tumor Biology, 2013, 34: 3791-3800.
[6] Zhang C Z, Zhang H, Yun J, et al. Dihydroartemisinin exhibits antitumor activity toward hepatocellular carcinoma in vitro and in vivo[J]. Biochemical pharmacology, 2012, 83(9): 1278-1289.
[7] Lu Z, Peng J H, Zhang R, et al. Dihydroartemisinin inhibits colon cancer cell viability by inducing apoptosis through up-regulation of PPARγ expression[J]. Saudi journal of biological sciences, 2018, 25(2): 372-376.

Dihydroartemisinin（双氢青蒿素；DHA）是青蒿素及其衍生物（ARTs）的活性代谢物，是临床广泛用于治疗疟疾的有效药物^[1]。Dihydroartemisinin通过抑制增殖、诱导细胞凋亡、抑制肿瘤转移和血管生成、促进免疫功能、诱导自噬和内质网应激等多种分子机制发挥抗癌作用^[2]。Dihydroartemisinin可以通过Fe(II)介导的内过氧化物裂解发挥细胞毒性作用^[3]。

在体外，Dihydroartemisinin（2.5-120μM）处理食管癌细胞（Eca109和Ec9706细胞）48和72h，以剂量依赖性方式降低了细胞活力，IC₅₀值分别为76.86μM和93.81μM，诱导了细胞凋亡和细胞周期阻滞^[4]。Dihydroartemisinin（0-80µM）处理胃癌细胞（SGC-7901，BGC823，和MGC803细胞）48和72h，以剂量依赖性方式降低了细胞活力，诱导了细胞G1期停滞、细胞凋亡和衰老^[5]。

在体内，Dihydroartemisinin（20mg/kg）通过腹腔注射治疗接种了人肝癌细胞（HepG2）的小鼠4周，显著抑制了肿瘤的生长，诱导了肿瘤组织细胞凋亡^[6]。Dihydroartemisinin（20mg/kg）通过腹腔注射治疗结肠癌小鼠30天，显著抑制了结肠肿瘤形成，诱导了肿瘤组织细胞凋亡，增加了过氧化物酶体增殖物活化受体γ（PPARγ）的表达^[7]。