天然药用植物，又称草药，因其潜在的抗肿瘤和促长寿活性引起了相当多的研究关注。我们先前的综述提出，保持衰老与癌症之间的稳态平衡可能有益于机体实现无肿瘤的长寿。中国云南省边境生长的浙江金钟（CCM）是一种植物物种。目前对其药用价值的报告很少。因此，筛选和提取从CCM中具有活性的肿瘤抑制剂和TERT活化剂成分是改善无肿瘤长寿的治疗策略。本研究旨在提取和评估植物CCM的细胞毒性抗肿瘤和TERT转录促进活性。 从CCM中提取的成分被用于测试pGL4-p53-GFP细胞中p53的转录激活以及使用实时荧光定量PCR（real-time PCR）测定TERT的表达。采用SRB细胞增殖抑制率检测和Annexin V/PI染色检测体外抗肿瘤活性。利用细胞渗透性探针H2DCFDA检测细胞内活性氧自由基（ROS）。通过Western blot验证成分调控的预测蛋白质。采用RNA测序分析预测CCM的潜在机制。 CCM和MPRC2-8两种浙江金钟的新提取物均活化p53和TERT的表达，并对肿瘤细胞具有选择性毒性。此外，MPRC2-8的细胞毒性机制被识别为ROS生成引起的凋亡。有趣的是，MPRC2-8在具有不同p53状况的A549和HT-29 细胞中显示了对SIRT1-p53轴相反的调节效应。RNA测序分析显示，CCM和MPRC2-8诱导了p53、凋亡和ROS信号通路，与体外细胞实验结果一致。 我们的研究揭示了CCM和MPRC2-8具有互补的抗肿瘤活性和TERT激活活性，具有潜在的抗肿瘤和延长寿命的效果。版权所有 © 2023. Elsevier B.V. 发表。

Natural medicinal plants, also named herbs, have attracted considerable research attention for their potential pharmacological activities, such as antitumor and longevity-promoting activities. Our previous review proposed that maintaining the homeostatic balance between aging and cancer may benefit organisms to enable tumor-free longevity. Congea chinensis Moldenke (CCM) is a plant species that grows on the border of Yunnan Province of China. Its medicinal value has been few reports until now. Thus, screening and extraction the ingredients from CCM that are both active tumor suppressors and TERT activators is a therapeutic strategy for improving tumor-free longevity.To extract and evaluate the cytotoxic antitumor and TERT transcription-promoting activities of the plant CCM.The ingredients extracted from CCM were tested for transcriptional activation of p53 using pGL4-p53-GFP cells and for TERT expression using a real-time PCR assay. In vitro antitumor activity was detected by sulforhodamine B (SRB) assay and Annexin V/PI staining assay. The cell-permeable probe H2DCFDA was used to detect intracellular reactive oxygen species (ROS). Western blot was performed to verify predicated proteins regulated by the ingredients. RNA-sequence analysis was applied to predicate the underlying mechanism of CCM.Both CCM and MPRC2-8, two novel extracts of Congea chinensis Moldenke, activated the expression of p53 and TERT and were selectively cytotoxic toward tumor cells. In addition, the cytotoxic mechanism of MPRC2-8 was identified as ROS generation-induced apoptosis. Interestingly, MPRC2-8 showed opposite regulatory effects on the SIRT1-p53 axis in A549 and HT-29 cells, which have different p53 statuses. RNA-seq analysis showed that CCM and MPRC2-8 induced the p53, apoptosis and ROS signaling pathways, consistent with the results of cellular experiments in vitro.Our study reveals that CCM and MPRC2-8 have two complementary activities, antitumor activity and TERT-activating activity, with potential antitumor and longevity-improving effects.Copyright © 2023. Published by Elsevier B.V.