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The dual effects of Congea chinensis Moldenke on inhibiting tumor cell proliferation and delaying aging by activating TERT transcriptional activity

文献类型： 外文期刊

作者： Peng, Lei 1 ; Dan, Juhua 1 ; Huang, Wenhui 1 ; Sang, Lei 1 ; Tian, Hao 3 ; Li, Zhiming 3 ; Li, Wanyi 3 ; Liu, Jing 1 ; Luo, Ying 2 ;

作者机构： 1.Kunming Univ Sci & Technol, Med Sch, Lab Mol Genet Aging & Tumor, Kunming 650500, Peoples R China

2.Guizhou Med Univ, Sch Basic Med, Guizhou Prov Key Lab Pathogenesis & Drug Dev Commo, Guiyang, Peoples R China

3.Yunnan Acad Agr Sci, Inst Med Plants, Kunming 650200, Peoples R China

4.Guizhou Med Univ, Sch Basic Med, Guizhou Prov Key Lab Pathogenesis & Drug Dev Commo, Guiyang 550000, Guizhou, Peoples R China

5.Kunming Univ Sci & Technol, Med Sch, Lab Mol Genet Aging & Tumor, 727 South Jing Ming Rd, Kunming 650500, Yunnan, Peoples R China

6.Yunnan Acad Agr Sci, Inst Med Plants, Kunming 650200, Yunnan, Peoples R China

关键词： Congea chinensis Moldenke; Cytotoxic antitumor activity; Apoptosis; TERT

期刊名称：JOURNAL OF ETHNOPHARMACOLOGY （ 影响因子：5.4； 五年影响因子：5.3 ）

ISSN： 0378-8741

年卷期： 2024 年 319 卷

页码：

收录情况： SCI

摘要： Ethnopharmacological relevance: 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. Aim of the study: To extract and evaluate the cytotoxic antitumor and TERT transcription-promoting activities of the plant CCM. Materials and methods: 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. Results: 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. Conclusion: 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.

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