Bufadienolides are cardioactive C24 steroids with an α-pyrone ring at position C17. In the last ten years, accumulating studies have revealed the anticancer activities of bufadienolides and their underlying mechanisms, such as induction of autophagy and apoptosis, cell cycle disruption, inhibition of angiogenesis, epithelial-mesenchymal transition (EMT) and stemness, and multidrug resistance reversal. As Na⁺/K⁺-ATPase inhibitors, bufadienolides have inevitable cardiotoxicity. Short half-lives, poor stability, low plasma concentration and oral bioavailability in vivo are obstacles for their applications as drugs. To improve the drug potency of bufadienolides and reduce their side effects, prodrug strategies and drug delivery systems such as liposomes and nanoparticles have been applied. Therefore, systematic and recapitulated information about the antitumor activity of bufadienolides, with special emphasis on the molecular or cellular mechanisms, prodrug strategies and drug delivery systems, is of high interest. Here, we systematically review the anticancer effects of bufadienolides and the molecular or cellular mechanisms of action. Research advancements regarding bufadienolide prodrugs and their tumor-targeting delivery strategies are critically summarized. This work highlights recent scientific advances regarding bufadienolides as effective anticancer agents from 2011 to 2019, which will help researchers to understand the molecular pathways involving bufadienolides, resulting in a selective and safe new lead compound or therapeutic strategy with improved therapeutic applications of bufadienolides for cancer therapy.

丁二烯内酯是心脏活性的C24类固醇，在C17位带有一个α-吡喃酮环。在过去的十年中，不断积累的研究揭示了布法地烯内酯的抗癌活性及其潜在机制，例如自噬和凋亡的诱导，细胞周期破坏，血管生成的抑制，上皮-间质转化（EMT）和干性以及多药耐药性的逆转。作为Na ⁺ / K ⁺ -ATPase抑制剂，丁二烯内酯具有不可避免的心脏毒性。半衰期短，稳定性差，血浆浓度低和体内口服生物利用度是其作为药物应用的障碍。为了提高丁二烯内酯的药效并降低其副作用，已应用了前药策略和药物递送系统，例如脂质体和纳米颗粒。因此，关于布法地烯内酯的抗肿瘤活性的系统的和概括的信息，特别是分子或细胞机制，前药策略和药物递送系统，特别引起人们的关注。在这里，我们系统地审查了丁二烯内酯的抗癌作用以及作用的分子或细胞机制。关于布法地那利德前药及其靶向肿瘤的治疗策略的研究进展已被严格总结。这项工作着重说明了2011年至2019年间有关布非二烯内酯作为有效抗癌剂的最新科学进展，