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Proteomic Analysis of Human Breast Cancer MCF-7 Cells to Identify Cellular Targets of the Anticancer Pigment OR3 from Streptomyces coelicolor JUACT03

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Abstract

Search for ideal compounds with known pathways of anticancer mechanism is still a priority research focus for cancer, as it continues to be a major health challenge across the globe. Hence, in the present study, anticancer potential of a yellow pigment fraction, OR3, isolated from Streptomyces coelicolor JUACT03 was assessed on the breast cancer cell line MCF-7. TLC-fractionated OR3 pigment was subjected to HPLC and GC–MS analysis for characterization and identification of the bioactive component. MCF-7 cells were treated with IC50 concentration of OR3 and the molecular alterations were analyzed using mass spectrometry-based quantitative proteomic analysis. Bioinformatics tools such as STRING analysis and Ingenuity Pathway Analysis were performed to analyze proteomics data and to identify dysregulated signaling pathways. As per our obtained data, OR3 treatment decreased cell proliferation and induced apoptotic cell death due to significant dysregulation of protein expressions in MCF-7 cells. Altered expression included the ribosomal, mRNA processing and vesicle-mediated transport proteins as a result of OR3 treatment. Downregulation of MAPK proteins, NFkB, and estradiol signaling was identified in OR3-treated MCF-7 cells. Mainly eIF2, mTOR, and eIF4 signaling pathways were altered in OR3-treated cells. GC–MS data indicated the presence of novel compounds in OR3 fraction. It can be concluded that OR3 exhibits potent anticancer activity on the breast cancer cells mainly through altering the expression and affecting the signaling proteins which are involved in different cell proliferation/apoptotic pathways thereby causing inhibition of cancer cell proliferation, survival and metastasis.

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Data Availability

Raw MS files obtained in this experiment have been uploaded to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org), through the PRIDE partner repository with the dataset identifier PXD032999. Other datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Biotechnology, School of Sciences, JAIN (Deemed-to-Be-University), Bangalore, 560078, Karnataka, India

    Somasekhara D & Varalakshmi Kilingar Nadumane

  2. Department of Biotechnology, Siddaganga Institute of Technology, Tumakuru, 572103, India

    Manjunath Dammalli

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Contributions

Study conception and design by Varalakshmi K Nadumane. Material preparation, data collection, and analysis were performed by Somasekhara D; Proteomics study and analysis by Manjunath Dammalli. The first draft of the manuscript was written by Somasekhara D; and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Varalakshmi Kilingar Nadumane.

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D, S., Dammalli, M. & Nadumane, V.K. Proteomic Analysis of Human Breast Cancer MCF-7 Cells to Identify Cellular Targets of the Anticancer Pigment OR3 from Streptomyces coelicolor JUACT03. Appl Biochem Biotechnol 195, 236–252 (2023). https://doi.org/10.1007/s12010-022-04128-8

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