Transcriptomics and Proteomics Characterizing the Anticancer Mechanisms of Natural Rebeccamycin Analog Loonamycin in Breast Cancer Cells
The present study is to explore the anticancer effect of loonamycin (LM) in vitro and in vivo, and investigate the underlying mechanism with combined multi-omics. LM exhibited anticancer activity in human triple negative breast cancer cells by promoting cell apoptosis. LM administration inhibited th...
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MDPI AG
2022-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/20/6958 |
| _version_ | 1797470908289384448 |
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| author | Xiao Sun Zhanying Lu Zhenzhen Liang Bowen Deng Yuping Zhu Jing Shi Xiaoling Lu |
| author_facet | Xiao Sun Zhanying Lu Zhenzhen Liang Bowen Deng Yuping Zhu Jing Shi Xiaoling Lu |
| author_sort | Xiao Sun |
| collection | DOAJ |
| description | The present study is to explore the anticancer effect of loonamycin (LM) in vitro and in vivo, and investigate the underlying mechanism with combined multi-omics. LM exhibited anticancer activity in human triple negative breast cancer cells by promoting cell apoptosis. LM administration inhibited the growth of MDA-MB-468 tumors in a murine xenograft model of breast cancer. Mechanistic studies suggested that LM could inhibit the topoisomerase I in a dose-dependent manner in vitro experiments. Combined with the transcriptomics and proteomic analysis, LM has a significant effect on O-glycan, p53-related signal pathway and EGFR/PI3K/AKT/mTOR signal pathway in enrichment of the KEGG pathway. The GSEA data also suggests that the TNBC cells treated with LM may be regulated by p53, O-glycan and EGFR/PI3K/AKT/mTOR signaling pathway. Taken together, our findings predicted that LM may target p53 and EGFR/PI3K/AKT/mTOR signaling pathway, inhibiting topoisomerase to exhibit its anticancer effect. |
| first_indexed | 2024-03-09T19:42:36Z |
| format | Article |
| id | doaj.art-9f63f173fc2142d999e950b10c18db42 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T19:42:36Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-9f63f173fc2142d999e950b10c18db422023-11-24T01:34:34ZengMDPI AGMolecules1420-30492022-10-012720695810.3390/molecules27206958Transcriptomics and Proteomics Characterizing the Anticancer Mechanisms of Natural Rebeccamycin Analog Loonamycin in Breast Cancer CellsXiao Sun0Zhanying Lu1Zhenzhen Liang2Bowen Deng3Yuping Zhu4Jing Shi5Xiaoling Lu6Experimental Training Center of Basic Medical Science, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, ChinaExperimental Training Center of Basic Medical Science, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, ChinaDepartment of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, ChinaDepartment of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, ChinaExperimental Training Center of Basic Medical Science, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Life Sciences, Nanjing University, Nanjing 210023, ChinaDepartment of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, ChinaThe present study is to explore the anticancer effect of loonamycin (LM) in vitro and in vivo, and investigate the underlying mechanism with combined multi-omics. LM exhibited anticancer activity in human triple negative breast cancer cells by promoting cell apoptosis. LM administration inhibited the growth of MDA-MB-468 tumors in a murine xenograft model of breast cancer. Mechanistic studies suggested that LM could inhibit the topoisomerase I in a dose-dependent manner in vitro experiments. Combined with the transcriptomics and proteomic analysis, LM has a significant effect on O-glycan, p53-related signal pathway and EGFR/PI3K/AKT/mTOR signal pathway in enrichment of the KEGG pathway. The GSEA data also suggests that the TNBC cells treated with LM may be regulated by p53, O-glycan and EGFR/PI3K/AKT/mTOR signaling pathway. Taken together, our findings predicted that LM may target p53 and EGFR/PI3K/AKT/mTOR signaling pathway, inhibiting topoisomerase to exhibit its anticancer effect.https://www.mdpi.com/1420-3049/27/20/6958loonamycintriple negative breast cancerp53PI3K/AKT/mTORO-glycan |
| spellingShingle | Xiao Sun Zhanying Lu Zhenzhen Liang Bowen Deng Yuping Zhu Jing Shi Xiaoling Lu Transcriptomics and Proteomics Characterizing the Anticancer Mechanisms of Natural Rebeccamycin Analog Loonamycin in Breast Cancer Cells Molecules loonamycin triple negative breast cancer p53 PI3K/AKT/mTOR O-glycan |
| title | Transcriptomics and Proteomics Characterizing the Anticancer Mechanisms of Natural Rebeccamycin Analog Loonamycin in Breast Cancer Cells |
| title_full | Transcriptomics and Proteomics Characterizing the Anticancer Mechanisms of Natural Rebeccamycin Analog Loonamycin in Breast Cancer Cells |
| title_fullStr | Transcriptomics and Proteomics Characterizing the Anticancer Mechanisms of Natural Rebeccamycin Analog Loonamycin in Breast Cancer Cells |
| title_full_unstemmed | Transcriptomics and Proteomics Characterizing the Anticancer Mechanisms of Natural Rebeccamycin Analog Loonamycin in Breast Cancer Cells |
| title_short | Transcriptomics and Proteomics Characterizing the Anticancer Mechanisms of Natural Rebeccamycin Analog Loonamycin in Breast Cancer Cells |
| title_sort | transcriptomics and proteomics characterizing the anticancer mechanisms of natural rebeccamycin analog loonamycin in breast cancer cells |
| topic | loonamycin triple negative breast cancer p53 PI3K/AKT/mTOR O-glycan |
| url | https://www.mdpi.com/1420-3049/27/20/6958 |
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