College of Life Science, Northeast Forestry University, Harbin, Heilongjiang, 150040, PR China; Key Laboratory of Saline-alkali Vegetation Ecology Restoration, Ministry of Education, Harbin, Heilongjiang, 150040, PR China.
Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, PR, PR China.
Phytomedicine. 2024 Jun;128:155432. doi: 10.1016/j.phymed.2024.155432. Epub 2024 Feb 9.
Cancer, the second leading cause of death worldwide following cardiovascular diseases, presents a formidable challenge in clinical settings due to the extensive toxic side effects associated with primary chemotherapy drugs employed for cancer treatment. Furthermore, the emergence of drug resistance against specific chemotherapeutic agents has further complicated the situation. Consequently, there exists an urgent imperative to investigate novel anticancer drugs. Steroidal saponins, a class of natural compounds, have demonstrated notable antitumor efficacy. Nonetheless, their translation into clinical applications has remained unrealized thus far. In light of this, we conducted a comprehensive systematic review elucidating the antitumor activity, underlying mechanisms, and inherent limitations of steroidal saponins. Additionally, we propose a series of strategic approaches and recommendations to augment the antitumor potential of steroidal saponin compounds, thereby offering prospective insights for their eventual clinical implementation.
This review summarizes steroidal saponins' antitumor activity, mechanisms, and limitations.
The data included in this review are sourced from authoritative databases such as PubMed, Web of Science, ScienceDirect, and others.
A comprehensive summary of over 40 steroidal saponin compounds with proven antitumor activity, including their applicable tumor types and structural characteristics, has been compiled. These steroidal saponins can be primarily classified into five categories: spirostanol, isospirostanol, furostanol, steroidal alkaloids, and cholestanol. The isospirostanol and cholestanol saponins are found to have more potent antitumor activity. The primary antitumor mechanisms of these saponins include tumor cell apoptosis, autophagy induction, inhibition of tumor migration, overcoming drug resistance, and cell cycle arrest. However, steroidal saponins have limitations, such as higher cytotoxicity and lower bioavailability. Furthermore, strategies to address these drawbacks have been proposed.
In summary, isospirostanol and cholestanol steroidal saponins demonstrate notable antitumor activity and different structural categories of steroidal saponins exhibit variations in their antitumor signaling pathways. However, the clinical application of steroidal saponins in cancer treatment still faces limitations, and further research and development are necessary to advance their potential in tumor therapy.
癌症是全球仅次于心血管疾病的第二大死亡原因，在临床环境中构成了巨大挑战，因为用于癌症治疗的主要化疗药物存在广泛的毒性副作用。此外，针对特定化疗药物的耐药性的出现进一步使情况复杂化。因此，迫切需要研究新型抗癌药物。甾体皂苷作为一类天然化合物，表现出显著的抗肿瘤功效。然而，迄今为止，它们尚未转化为临床应用。有鉴于此，我们进行了一项全面的系统综述，阐明了甾体皂苷的抗肿瘤活性、潜在机制和固有局限性。此外，我们提出了一系列战略方法和建议，以增强甾体皂苷化合物的抗肿瘤潜力，从而为它们最终的临床应用提供前瞻性见解。
本综述总结了甾体皂苷的抗肿瘤活性、机制和局限性。
本综述的数据来源于PubMed、Web of Science、ScienceDirect 等权威数据库。
我们综合总结了 40 多种具有抗肿瘤活性的甾体皂苷化合物，包括它们适用的肿瘤类型和结构特征。这些甾体皂苷主要可分为五类：螺甾烷醇、异螺甾烷醇、呋甾烷醇、甾体生物碱和胆甾醇。异螺甾烷醇和胆甾醇皂苷被发现具有更强的抗肿瘤活性。这些皂苷的主要抗肿瘤机制包括肿瘤细胞凋亡、自噬诱导、抑制肿瘤迁移、克服耐药性和细胞周期停滞。然而，甾体皂苷存在局限性，如更高的细胞毒性和较低的生物利用度。此外，还提出了一些解决这些缺点的策略。
综上所述，异螺甾烷醇和胆甾醇甾体皂苷具有显著的抗肿瘤活性，不同结构类别的甾体皂苷在其抗肿瘤信号通路中表现出差异。然而，甾体皂苷在癌症治疗中的临床应用仍面临局限性，需要进一步的研究和开发，以推进其在肿瘤治疗中的潜力。
