Advances in antitumor activity and mechanism of natural steroidal saponins: A review of advances, challenges, and future prospects

Wang, Fengge, Liang, Lu, Yu, Ma, Wang, Wenjie, Badar, Iftikhar Hussain, Bao, Yongping ORCID: https://orcid.org/0000-0002-6425-0370, Zhu, Kai, Li, Yanlin, Shafi, Saba, Li, Dangdang, Diao, Yongchao, Efferth, Thomas, Xue, Zheyong and Hua, Xin (2024) Advances in antitumor activity and mechanism of natural steroidal saponins: A review of advances, challenges, and future prospects. Phytomedicine, 128. ISSN 0944-7113

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Abstract

Background: 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. Purpose: This review summarizes steroidal saponins' antitumor activity, mechanisms, and limitations. Methods: The data included in this review are sourced from authoritative databases such as PubMed, Web of Science, ScienceDirect, and others. Results: 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. Conclusion: 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.

Item Type:	Article
Additional Information:	Funding information: This work was supported by the National Key Research and Development Program of China (Grant No.2023YFA0915800), Key project at central government level: The ability establishment of sustainable use for valuable Chinese medicine resources (2060302); and the National Natural Science Foundation of China (Grant No.U23A2051).
Uncontrolled Keywords:	antitumor mechanisms,cancer,phytochemistry,phytotherapy,steroidal saponins,drug discovery,molecular medicine,complementary and alternative medicine,pharmacology,pharmaceutical science,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/3000/3002
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	04 Mar 2024 18:32
Last Modified:	09 Apr 2024 09:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/94500
DOI:	10.1016/j.phymed.2024.155432

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