Saikosaponins Targeting Programmed Cell Death as Anticancer Agents: Mechanisms and Future Perspectives.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL Drug Design, Development and Therapy Pub Date : 2024-08-21 eCollection Date: 2024-01-01 DOI:10.2147/DDDT.S470455

Xiao Xiao, Chunfang Gao

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Abstract

Saikosaponins (SS), which are major bioactive compounds in Radix Bupleuri, have long been used clinically for multicomponent, multitarget, and multipathway therapeutic strategies. Programmed cell death (PCD) induction is among the multiple mechanisms of SS and mediates the anticancer efficacy of this drug family. Although SS show promise for anticancer therapy, the available data to explain how SS mediate their key anticancer effects through PCD (apoptosis, autophagy, ferroptosis, and pyroptosis) remain limited and piecemeal. This review offers an extensive analysis of the key pathways and mechanisms involved in PCD and explores the importance of SS in cancer. We believe that high-quality clinical trials and a deeper understanding of the pharmacological targets involved in the signalling cascades that govern tumour initiation and progression are needed to facilitate the development of innovative SS-based treatments. Elucidating the specific anticancer pathways activated by SS and further clarifying how comprehensive therapies lead to cross-link among the different types of cell death will inspire the clinical translation of SS as cancer treatments.

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以程序性细胞死亡为靶点的赛可皂甙类抗癌药物：机制与未来展望》。

柴胡皂苷（SS）是柴胡中的主要生物活性化合物，长期以来一直被临床用于多成分、多靶点和多途径的治疗策略。诱导细胞程序性死亡（PCD）是 SS 的多种机制之一，也是该药物家族抗癌功效的介导因素。虽然固醇类药物有望用于抗癌治疗，但现有的数据仍很有限，无法解释固醇类药物如何通过 PCD（细胞凋亡、自噬、铁凋亡和热凋亡）介导其主要的抗癌作用。本综述广泛分析了参与 PCD 的关键途径和机制，并探讨了 SS 在癌症中的重要性。我们认为，需要进行高质量的临床试验，并深入了解控制肿瘤发生和发展的信号级联所涉及的药理学靶点，以促进基于 SS 的创新疗法的开发。阐明由 SS 激活的特定抗癌途径并进一步阐明综合疗法如何导致不同类型细胞死亡之间的交叉联系，将激励 SS 作为癌症治疗方法的临床转化。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.