Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, China.
Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China.
Biomater Sci. 2024 Nov 5;12(22):5656-5679. doi: 10.1039/d4bm01023j.
Natural products, which are compounds extracted and/or refined from plants and microbes in nature, have great potential for the discovery of therapeutic agents, especially for infectious diseases and cancer. In recent years, natural products have been reported to induce multiple cell death pathways to exhibit antitumor effects. Among them, pyroptosis is a unique programmed cell death (PCD) characterized by continuous cell membrane permeability and intracellular content leakage. According to the canonical and noncanonical pathways, the formation of gasdermin-N pores involves a variety of transcriptional targets and post-translational modifications. Thus, tailored control of PCD may facilitate dying cells with sufficient immunogenicity to activate the immune system to eliminate other tumor cells. Therefore, we summarized the currently reported natural products or their derivatives and their nano-drugs that induce pyroptosis-related signaling pathways. We reviewed six main categories of bioactive compounds extracted from natural products, including flavonoids, terpenoids, polyphenols, quinones, artemisinins, and alkaloids. Correspondingly, the underlying mechanisms of how these compounds and their derivatives engage in pyroptosis are also discussed. Moreover, the synergistic effect of natural bioactive compounds with other antitumor therapies is proposed as a novel therapeutic strategy for traditional chemotherapy, radiotherapy, chemodynamic therapy, photodynamic therapy, photothermal therapy, hyperthermal therapy, and sonodynamic therapy. Consequently, we provide insights into natural products to develop a novel antitumor therapy or qualified adjuvant agents by inducing pyroptosis, which may eventually be applied clinically.
天然产物是从自然界中的植物和微生物中提取和/或精制的化合物，具有发现治疗剂的巨大潜力，特别是针对传染病和癌症。近年来，天然产物已被报道可诱导多种细胞死亡途径来发挥抗肿瘤作用。其中，细胞焦亡是一种独特的程序性细胞死亡（PCD），其特征是细胞膜持续通透性和细胞内内容物泄漏。根据经典和非经典途径，gasdermin-N 孔的形成涉及多种转录靶标和翻译后修饰。因此，对 PCD 的精确控制可能有助于具有足够免疫原性的死亡细胞激活免疫系统以消除其他肿瘤细胞。因此，我们总结了目前报道的天然产物或其衍生物及其诱导细胞焦亡相关信号通路的纳米药物。我们回顾了从天然产物中提取的六大类生物活性化合物，包括黄酮类、萜类、多酚类、醌类、青蒿素和生物碱。相应地，还讨论了这些化合物及其衍生物如何参与细胞焦亡的潜在机制。此外，还提出了天然生物活性化合物与其他抗肿瘤疗法的协同作用作为传统化疗、放疗、化学动力学疗法、光动力疗法、光热疗法、高热疗法和声动力疗法的一种新的治疗策略。因此，我们通过诱导细胞焦亡为开发新型抗肿瘤疗法或合格的佐剂提供了天然产物的见解，这最终可能会在临床上得到应用。
