Abdelmoaty Ahmed Attia Ahmed, Chen Jing, Zhang Kun, Wu Changhui, Li Ye, Li Peng, Xu Jianhua
Fujian Provincial Key Laboratory of Pharmacology of Natural Medicine, School of Pharmacy, Fujian Medical University, Fuzhou, China.
Fujian Xianzhilou Biological Science and Technology Co., Ltd., Fuzhou, China.
Front Pharmacol. 2024 Sep 19;15:1422363. doi: 10.3389/fphar.2024.1422363. eCollection 2024.
() is a famous medicinal mushroom that has been reported to prevent and treat a variety of diseases. Different extractions from have been used to manage age-related diseases, including cancer. Nevertheless, the senolytic activity of against senescent cancer cells has not been investigated. Although cellular senescence causes tumor growth inhibition, senescent cells promote the growth of the neighboring tumor cells through paracrine effects. Therefore, the elimination of senescent cells is a new strategy for cancer treatment.
In this study, senescence was triggered in HCC cells by the chemotherapeutic agent Adriamycin (ADR), and subsequently, cells were treated with TC to assess its senolytic activity.
We found for the first time that the triterpenoid complex (TC) from had senolytic effect, which could selectively eliminate adriamycin (ADR)-induced senescent cells (SCs) of hepatocellular carcinoma (HCC) cells via caspase-dependent and mitochondrial pathways-mediated apoptosis and reduce the levels of senescence markers, thereby inhibiting the progression of cancers caused by SCs. TC could block autophagy at the late stage in SCs, resulting in a significant activation of TC-induced apoptosis. Furthermore, TC inhibited the senescence-associated secretory phenotype (SASP) in SCs through the inhibition of NF-κB, TFEB, P38, ERK, and mTOR signaling pathways and reducing the number of SCs. Sequential administration of ADR and TC significantly reduced tumor growth and reversed the toxicity of ADR.
A triterpenoid complex isolated from may serve as a novel senolytic agent against SCs, and its combination with chemotherapeutic agents may enhance their antitumor efficacy.
（某种蘑菇名称未给出）是一种著名的药用蘑菇，据报道可预防和治疗多种疾病。该蘑菇的不同提取物已被用于管理与年龄相关的疾病，包括癌症。然而，其对衰老癌细胞的溶衰老活性尚未得到研究。尽管细胞衰老会导致肿瘤生长抑制，但衰老细胞通过旁分泌作用促进邻近肿瘤细胞的生长。因此，消除衰老细胞是一种新的癌症治疗策略。
在本研究中，用化疗药物阿霉素（ADR）诱导肝癌细胞发生衰老，随后用（该蘑菇提取物）TC处理细胞以评估其溶衰老活性。
我们首次发现来自（该蘑菇）的三萜类化合物复合物（TC）具有溶衰老作用，它可以通过半胱天冬酶依赖性和线粒体途径介导的凋亡选择性地消除阿霉素（ADR）诱导的肝癌（HCC）细胞衰老细胞（SCs），并降低衰老标志物水平，从而抑制由SCs引起的癌症进展。TC可在SCs的后期阻断自噬，导致TC诱导的凋亡显著激活。此外，TC通过抑制NF-κB、TFEB、P38、ERK和mTOR信号通路并减少SCs数量，抑制SCs中的衰老相关分泌表型（SASP）。序贯给予ADR和TC可显著降低肿瘤生长并逆转ADR的毒性。
从（该蘑菇）中分离出的三萜类化合物复合物可能作为一种新型的针对SCs的溶衰老剂，其与化疗药物联合使用可能增强它们的抗肿瘤疗效。
