Anticancer Potential of Atractylenolides I-III: Efficacy, Mechanisms, Pharmacokinetics, and Safety

Atractylenolides (ATs; mainly AT-I, II, and III), as one of the primary active components of the traditional Chinese medicine Atractylodes macrocephala, have demonstrated significant antitumorigenic effects against various cancer cells in both in vitro and in vivo studies. This review aims to systematically review the antitumorigenic effects, mechanisms, pharmacokinetics, and safety profile of ATs, aiming to contribute to clinical research and applications. To achieve this, a systematic literature search was conducted across multiple databases, and findings were synthesized narratively to provide a comprehensive overview of the current evidence. This review comprehensively discusses the antitumorigenic effects and mechanisms of ATs, including arresting tumor cell cycle progression, inducing programmed cell death (apoptosis, autophagy, and ferroptosis), inhibiting tumor angiogenesis, suppressing tumor migration and invasion, modulating the tumor immune microenvironment, and enhancing the efficacy of combination therapies. Additionally, their pharmacokinetic properties and safety profile are summarized, with a focus on their research and application prospects. ATs appear to be safe and reliable candidate anticancer agents in preclinical models, exhibiting potent antitumor efficacy both as monotherapy and in combination regimens. Preliminary clinical data from a small pilot study also indicated no signs of toxicity, but more extensive trials are needed to confirm their safety profile in humans. Further studies on their mechanisms are warranted to facilitate their development into clinically effective antitumor agents.