Transcriptomics and Proteomics Characterizing the Anticancer Mechanisms of Natural Rebeccamycin Analog Loonamycin in Breast Cancer Cells.

Abstract

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.

• Authors: Xiao Sun, Zhanying Lu, Zhenzhen Liang, Bowen Deng, Yuping Zhu, Jing Shi, Xiaoling Lu
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 27 Issue 20 (Oct 17 2022) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 36296549 (Publication Type: Journal Article)

Chemical References

• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• rebeccamycin
• DNA Topoisomerases, Type I
• Tumor Suppressor Protein p53
• TOR Serine-Threonine Kinases
• ErbB Receptors

Topics

• Humans
• Mice
• Animals
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• DNA Topoisomerases, Type I (metabolism)
• Tumor Suppressor Protein p53 (genetics, metabolism)
• Transcriptome
• Proteomics
• Cell Line, Tumor
• TOR Serine-Threonine Kinases (metabolism)
• Triple Negative Breast Neoplasms (metabolism)
• Apoptosis
• ErbB Receptors (genetics, metabolism)
• Cell Proliferation