A mass spectrometry-based proteome map of drug action in lung cancer cell lines

Ruprecht, Benjamin; Bernardo, Julie Di; Wang, Zhao; Mo, Xuan; Ursu, Oleg; Christopher, Matthew; Fernández, Rafael; Zheng, Li; Dill, Brian D.; Wang, Huijun; Xu, Yuting; Liaw, Andy; Mortison, Jonathan D.; Siriwardana, Nirodhini; Andresen, Brian M.; Glick, Meir; Tata, James R.; Kutilek, Victoria; Cornella-Taracido, Ivan; Chen, An

doi:10.1038/s41589-020-0572-3

Cited by 42 publications

(48 citation statements)

References 47 publications

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“…Aiming at the drug development, several groups have used proteomics approach to observe up- or down-regulated effects of proteins resulting from disease activity or side effects of the treatments [ 44 , 45 , 128 , 129 , 130 , 131 ]. Moreover, the quest for the identification of biological markers or biomarkers using venom that may help in the early detection of pathologies such as cancer, and the quest for products able to evaluate the metastatic potential and propose new forms of treatment to tumors, remains an important goal of research groups and pharmaceutical companies.…”

Section: Discussionmentioning

confidence: 99%

“…A number of studies have characterized the biochemical and physiological action of venom or isolated venom derivatives on cell lines or tissues [ 40 , 41 , 42 , 43 ]. In addition, several works have shown proteomic changes of cancer cell lines upon drug treatment that suggest molecular mechanisms of drug action, including diverse effects on proteasome regulation, metabolic processes, and oxidative stress [ 44 , 45 ].…”

Section: Introductionmentioning

confidence: 99%

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Bothrops Jararaca Snake Venom Modulates Key Cancer-Related Proteins in Breast Tumor Cell Lines

Kisaki

Arcos

Montoni

et al. 2021

Toxins

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Cancer is characterized by the development of abnormal cells that divide in an uncontrolled way and may spread into other tissues where they may infiltrate and destroy normal body tissue. Several previous reports have described biochemical anti-tumorigenic properties of crude snake venom or its components, including their capability of inhibiting cell proliferation and promoting cell death. However, to the best of our knowledge, there is no work describing cancer cell proteomic changes following treatment with snake venoms. In this work we describe the quantitative changes in proteomics of MCF7 and MDA-MB-231 breast tumor cell lines following treatment with Bothrops jararaca snake venom, as well as the functional implications of the proteomic changes. Cell lines were treated with sub-toxic doses at either 0.63 μg/mL (low) or 2.5 μg/mL (high) of B. jararaca venom for 24 h, conditions that cause no cell death per se. Proteomics analysis was conducted on a nano-scale liquid chromatography coupled on-line with mass spectrometry (nLC-MS/MS). More than 1000 proteins were identified and evaluated from each cell line treated with either the low or high dose of the snake venom. Protein profiling upon venom treatment showed differential expression of several proteins related to cancer cell metabolism, immune response, and inflammation. Among the identified proteins we highlight histone H3, SNX3, HEL-S-156an, MTCH2, RPS, MCC2, IGF2BP1, and GSTM3. These data suggest that sub-toxic doses of B. jararaca venom have potential to modulate cancer-development related protein targets in cancer cells. This work illustrates a novel biochemical strategy to identify therapeutic targets against cancer cell growth and survival.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bothrops Jararaca Snake Venom Modulates Key Cancer-Related Proteins in Breast Tumor Cell Lines

Kisaki

Arcos

Montoni

et al. 2021

Toxins

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“…The Multiplexed Proteome Dynamics Profiling (mPDP) workflow further allows additional differentiation of direct compound-induced protein degradation from downstream effects and has been used, e.g., to compare the effects of the heterobifunctional JQ1-VHL degrader vs. the bromodomain inhibitor JQ1 alone [120]. Recent advances in high-throughput sample preparation and data acquisition including the BoxCar method [121] have also allowed the rapid recording of compound-induced changes at the global proteome level [122] or for a set of phosphorylation sites (P100) [123] as signatures to derive compound MoA hypotheses either directly or via correlation to signatures of compounds with known MoA, akin to e.g. transcriptional approaches like L1000 [124].…”

Section: Other Proteomic Approaches For Target Identification and Moa Elucidationmentioning

confidence: 99%

Proteomics in the pharmaceutical and biotechnology industry: a look to the next decade

Lill¹,

Mathews²,

Rose³

et al. 2021

Expert Review of Proteomics

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Introduction: Pioneering technologies such as proteomics have helped fuel the biotechnology and pharmaceutical industry with the discovery of novel targets and an intricate understanding of the activity of therapeutics and their various activities in vitro and in vivo. The field of proteomics is undergoing an inflection point, where new sensitive technologies are allowing intricate biological pathways to be better understood, and novel biochemical tools are pivoting us into a new era of chemical proteomics and biomarker discovery. In this review, we describe these areas of innovation, and discuss where the fields are headed in terms of fueling biotechnological and pharmacological research and discuss current gaps in the proteomic technology landscape. Areas Covered: Single cell sequencing and single molecule sequencing. Chemoproteomics. Biological matrices and clinical samples including biomarkers. Computational tools including instrument control software, data analysis. Expert Opinion: Proteomics will likely remain a key technology in the coming decade, but will have to evolve with respect to type and granularity of data, cost and throughput of data generation as well as integration with other technologies to fulfill its promise in drug discovery.

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“… 76 The anaplastic lymphoma kinase (ALK) inhibitor ceritinib was found to be capable of modulating the protein-trafficking and degradation-related process of autophagy after the quantitative analysis of five lung cancer cell lines in response to more than 50 drugs. 77 The proto-oncogene serine/threonine-protein kinase PIM3 has been widely used as a drug target. Quantitative phosphoproteomics revealed that PIM3 activated RhoA to promote migration and invasion of hepatoma cells.…”

Section: Discovering Drug Targets With Quantitative Proteomicsmentioning

confidence: 99%

Quantitative proteomics characterization of cancer biomarkers and treatment

Yang

Shi

Zhang

et al. 2021

Molecular Therapy - Oncolytics

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Cancer accounted for 16% of all death worldwide in 2018. Significant progress has been made in understanding tumor occurrence, progression, diagnosis, treatment, and prognosis at the molecular level. However, genomics changes cannot truly reflect the state of protein activity in the body due to the poor correlation between genes and proteins. Quantitative proteomics, capable of quantifying the relatively different protein abundance in cancer patients, has been increasingly adopted in cancer research. Quantitative proteomics has great application potentials, including cancer diagnosis, personalized therapeutic drug selection, real-time therapeutic effects and toxicity evaluation, prognosis and drug resistance evaluation, and new therapeutic target discovery. In this review, the development, testing samples, and detection methods of quantitative proteomics are introduced. The biomarkers identified by quantitative proteomics for clinical diagnosis, prognosis, and drug resistance are reviewed. The challenges and prospects of quantitative proteomics for personalized medicine are also discussed.

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A mass spectrometry-based proteome map of drug action in lung cancer cell lines

Cited by 42 publications

References 47 publications

Bothrops Jararaca Snake Venom Modulates Key Cancer-Related Proteins in Breast Tumor Cell Lines

Bothrops Jararaca Snake Venom Modulates Key Cancer-Related Proteins in Breast Tumor Cell Lines

Proteomics in the pharmaceutical and biotechnology industry: a look to the next decade

Quantitative proteomics characterization of cancer biomarkers and treatment

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