{"title":"源自土壤的链霉菌的色霉素通过靶向 c-FLIP 抑制人类非小细胞肺癌细胞的生长。","authors":"Gao-Jie Li, Chen Wang, Wen-Die Wang, Yue Shang, Chao-Yang Zeng, Ai-Min Wang, Jing-Lin Bai, Jing Su, Ling Su, Shu-Yi Si, Li-Yan Yu, Mao-Luo Gan, Shu-Zhen Chen","doi":"10.1080/10286020.2024.2375288","DOIUrl":null,"url":null,"abstract":"<p><p>Three chromomycin derivatives, chromomycins A<sub>3</sub> (<b>1,</b> CA<sub>3</sub>), A<sub>5</sub> (<b>2,</b> CA<sub>5</sub>), and monodeacetylchromomycin A<sub>3</sub> (<b>3,</b> MDA-CA<sub>3</sub>), were identified from the soil-derived <i>Streptomyces</i> sp. CGMCC 26516. A reinvestigation of the structure of CA<sub>5</sub> is reported, of which the absolute configuration was unambiguously determined for the first time to be identical with that of CA<sub>3</sub> based on nuclear magnetic resonance (NMR) data analysis as well as NMR and electronic circular dichroism calculations. Compounds <b>1-3</b> showed potent cytotoxicity against the non-small-cell lung cancer (NSCLC) cells (A549, H460, H157-c-FLIP, and H157-LacZ) and down-regulated the protein expression of c-FLIP in A549 cells. The IC<sub>50</sub> values of chromomycins in H157-c-FLIP were higher than that in H157-LacZ. Furthermore, si-c-FLIP promoted anti-proliferation effect of chromomycins in NSCLC cells. In nude mice xenograft model, <b>1</b> and <b>2</b> both showed more potent inhibition on the growth of H157-lacZ xenografts than that of H157-c-FLIP xenografts. These results verify that c-FLIP mediates the anticancer effects of chromomycins in NSCLC.</p>","PeriodicalId":15180,"journal":{"name":"Journal of Asian Natural Products Research","volume":null,"pages":null},"PeriodicalIF":1.3000,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Chromomycins from soil-derived <i>Streptomyces</i> sp. inhibit the growth of human non-small cell lung cancer cells by targeting c-FLIP.\",\"authors\":\"Gao-Jie Li, Chen Wang, Wen-Die Wang, Yue Shang, Chao-Yang Zeng, Ai-Min Wang, Jing-Lin Bai, Jing Su, Ling Su, Shu-Yi Si, Li-Yan Yu, Mao-Luo Gan, Shu-Zhen Chen\",\"doi\":\"10.1080/10286020.2024.2375288\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Three chromomycin derivatives, chromomycins A<sub>3</sub> (<b>1,</b> CA<sub>3</sub>), A<sub>5</sub> (<b>2,</b> CA<sub>5</sub>), and monodeacetylchromomycin A<sub>3</sub> (<b>3,</b> MDA-CA<sub>3</sub>), were identified from the soil-derived <i>Streptomyces</i> sp. CGMCC 26516. A reinvestigation of the structure of CA<sub>5</sub> is reported, of which the absolute configuration was unambiguously determined for the first time to be identical with that of CA<sub>3</sub> based on nuclear magnetic resonance (NMR) data analysis as well as NMR and electronic circular dichroism calculations. Compounds <b>1-3</b> showed potent cytotoxicity against the non-small-cell lung cancer (NSCLC) cells (A549, H460, H157-c-FLIP, and H157-LacZ) and down-regulated the protein expression of c-FLIP in A549 cells. The IC<sub>50</sub> values of chromomycins in H157-c-FLIP were higher than that in H157-LacZ. Furthermore, si-c-FLIP promoted anti-proliferation effect of chromomycins in NSCLC cells. In nude mice xenograft model, <b>1</b> and <b>2</b> both showed more potent inhibition on the growth of H157-lacZ xenografts than that of H157-c-FLIP xenografts. These results verify that c-FLIP mediates the anticancer effects of chromomycins in NSCLC.</p>\",\"PeriodicalId\":15180,\"journal\":{\"name\":\"Journal of Asian Natural Products Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2024-07-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Asian Natural Products Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/10286020.2024.2375288\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, APPLIED\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Asian Natural Products Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/10286020.2024.2375288","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}
Chromomycins from soil-derived Streptomyces sp. inhibit the growth of human non-small cell lung cancer cells by targeting c-FLIP.
Three chromomycin derivatives, chromomycins A3 (1, CA3), A5 (2, CA5), and monodeacetylchromomycin A3 (3, MDA-CA3), were identified from the soil-derived Streptomyces sp. CGMCC 26516. A reinvestigation of the structure of CA5 is reported, of which the absolute configuration was unambiguously determined for the first time to be identical with that of CA3 based on nuclear magnetic resonance (NMR) data analysis as well as NMR and electronic circular dichroism calculations. Compounds 1-3 showed potent cytotoxicity against the non-small-cell lung cancer (NSCLC) cells (A549, H460, H157-c-FLIP, and H157-LacZ) and down-regulated the protein expression of c-FLIP in A549 cells. The IC50 values of chromomycins in H157-c-FLIP were higher than that in H157-LacZ. Furthermore, si-c-FLIP promoted anti-proliferation effect of chromomycins in NSCLC cells. In nude mice xenograft model, 1 and 2 both showed more potent inhibition on the growth of H157-lacZ xenografts than that of H157-c-FLIP xenografts. These results verify that c-FLIP mediates the anticancer effects of chromomycins in NSCLC.
期刊介绍：
The Journal of Asian Natural Products Research (JANPR) publishes chemical and pharmaceutical studies in the English language in the field of natural product research on Asian ethnic medicine. The journal publishes work from scientists in Asian countries, e.g. China, Japan, Korea and India, including contributions from other countries concerning natural products of Asia. The journal is chemistry-orientated. Major fields covered are: isolation and structural elucidation of natural constituents (including those for non-medical uses), synthesis and transformation (including biosynthesis and biotransformation) of natural products, pharmacognosy, and allied topics. Biological evaluation of crude extracts are acceptable only as supporting data for pure isolates with well-characterized structures.
All published research articles in this journal have undergone rigorous peer review, based on initial editor screening and anonymized refereeing by at least two expert referees.
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