Artesunate: A potential drug for the prevention and treatment from hepatitis to hepatocellular carcinoma
Xinyue Liu, Yilin Cai, Yuanhao Zhang, Hetian Zhang, Sisi Tian, Yuxia Gong, Qin Song, Xiaotong Chen, Xiao Ma, Yueqiang Wen, Yu Chen, Jinhao Zeng
Abstract
Liver cancer represents a multifactorial, multistage, and intricately progressive malignancy. Over the past decade, artesunate (ART), initially renowned for its anti-malarial efficacy, has been the focus of over 3000 studies uncovering its diverse pharmacological actions, including anti-inflammatory, immunoregulatory, metabolic regulatory, anti-fibrotic, and anti-cancer properties. This review highlights ART's role in the multistep progression from hepatitis to cancer and its underlying regulatory mechanisms, revealing signal transducer and activator of transcription 3 (STAT3) and ferroptosis (a novel form of programmed cell death) as promising therapeutic targets. ART demonstrates efficacy in inhibiting hepatitis virus infections, modulating inflammation, and facilitating recovery from inflammatory processes. During stages of hepatic fibrosis or cirrhosis, ART reverses fibrotic and cirrhotic changes by suppressing hepatic stellate cell activity, regulating inflammatory pathways, inhibiting hematopoietic stem cell proliferation, and inducing ferroptosis. Additionally, ART hinders hepatocellular carcinoma (HCC) cell proliferation, invasion, and metastasis, induces apoptosis and autophagy, combats drug resistance, and enhances chemosensitivity. Collectively, ART exhibits multi-step actions across multiple targets and signaling pathways, highlighting its potential as a clinical candidate for the prevention and treatment of liver cancer, from hepatitis and hepatic fibrosis to advanced HCC.