Chemopreventive Agents Attenuate Rapid Inhibition of Gap Junctional Intercellular Communication Induced by Environmental Toxicants

Babica, Pavel; Čtveráčková, Lucie; Lenčešová, Zuzana; Trosko, James E.; Upham, Brad L.

doi:10.1080/01635581.2016.1180409

Cited by 16 publications

(13 citation statements)

References 43 publications

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“…www.nature.com/scientificreports www.nature.com/scientificreports/ malignant cells) or under experimentally induced chemical stress, diseased-conditions (e.g. tumor promoting, inflammatory) 14,15,71,72 .…”

Section: Discussionmentioning

confidence: 99%

Improved multiparametric scrape loading-dye transfer assay for a simultaneous high-throughput analysis of gap junctional intercellular communication, cell density and viability

Dydowiczová

Brózman

Babica

et al. 2020

Sci Rep

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Gap junctional intercellular communication (GJic) is a vital cellular process required for maintenance of tissue homeostasis. In vitro assessment of GJic represents valuable phenotypic endpoint that could be effectively utilized as an integral component in modern toxicity testing, drug screening or biomedical in vitro research. However, currently available methods for quantifying GJic with higher-throughputs typically require specialized equipment, proprietary software and/or genetically engineered cell models. to overcome these limitations, we present here an innovative adaptation of traditional, fluorescence microscopy-based scrape loading-dye transfer (SL-DT) assay, which has been optimized to simultaneously evaluate GJic, cell density and viability. this multiparametric method was demonstrated to be suitable for various multiwell microplate formats, which facilitates an automatized image acquisition. The assay workflow is further assisted by an open source-based software tools for batch image processing, analysis and evaluation of GJic, cell density and viability. our results suggest that this approach provides a simple, fast, versatile and cost effective way for in vitro high-throughput assessment of GJic and other related phenotypic cellular events, which could be included into in vitro screening and assessment of pharmacologically and toxicologically relevant compounds. Gap junctional intercellular communication (GJIC) allows an exchange of low molecular weight molecules (<1.2 kDa) between adjacent cells in both vertebrates and invertebrates 1. GJIC is mediated through intercellular channels build from connexin proteins in vertebrates and from innexin proteins in invertebrates 1,2. GJIC plays a central role in coordinating cell-to-cell communication and integration of signal transduction pathways controlling gene expression and cell behaviour in order to receive coordinated and collective responses from the cells across a tissue of multicellular organism 3,4. Dysregulation of GJIC and GJIC-dependent signal integration, for example by drugs or environmental contaminants, can disrupt the normal homeostatic control of a cell behaviour and lead to numerous adverse outcomes such as cardiovascular 5 , pulmonary 6 or reproductive system 7,8 diseases and cancer 4,9,10. On the other hand, timed and targeted upregulation or downregulation of GJIC, connexin channel or hemichannel activity, induced by pharmacological agents, is currently widely discussed as potential therapeutic approach for treatment of various diseases 10-12. Accordingly, GJIC can be effectively utilized in the modern toxicological and pharmacological research, and GJIC analysis could be a valuable component of any biological study. However, in vitro assessment of GJIC has been used relatively less frequently in the modern research in comparison to other and more traditional phenotypic assays, such as evaluation of cellular metabolic activity, cell proliferation, cell cycle, autophagy, apoptosis, cell migration, cytoskeletal rearangements 13. This m...

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Section: Discussionmentioning

confidence: 99%

Improved multiparametric scrape loading-dye transfer assay for a simultaneous high-throughput analysis of gap junctional intercellular communication, cell density and viability

Dydowiczová

Brózman

Babica

et al. 2020

Sci Rep

Self Cite

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“…Additional studies tried to reveal a chemopreventive effect using antioxidant substances, such as all-trans-retinoic acid (ATRA), lycopene, curcumin, etc. ; recently, Babica et al [49] proposed a method to screen a chemical with potential chemopreventive activity based on GJIC measurements.…”

Section: Gj Gjic and Cancermentioning

confidence: 99%

Gap Junction Intercellular Communication in the Carcinogenesis Hallmarks: Is This a Phenomenon or Epiphenomenon?

Zefferino

Piccoli

Gioia

et al. 2019

Cells

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If occupational tumors are excluded, cancer causes are largely unknown. Therefore, it appeared useful to work out a theory explaining the complexity of this disease. More than fifty years ago the first demonstration that cells communicate with each other by exchanging ions or small molecules through the participation of connexins (Cxs) forming Gap Junctions (GJs) occurred. Then the involvement of GJ Intercellular Communication (GJIC) in numerous physiological cellular functions, especially in proliferation control, was proven and accounts for the growing attention elicited in the field of carcinogenesis. The aim of the present paper is to verify and discuss the role of Cxs, GJs, and GJIC in cancer hallmarks, pointing on the different involved mechanisms in the context of the multi-step theory of carcinogenesis. Functional GJIC acts both as a tumor suppressor and as a tumor enhancer in the metastatic stage. On the contrary, lost or non-functional GJs allow the uncontrolled proliferation of stem/progenitor initiated cells. Thus, GJIC plays a key role in many biological phenomena or epiphenomena related to cancer. Depending on this complexity, GJIC can be considered a tumor suppressor in controlling cell proliferation or a cancer ally, with possible preventive or therapeutic implications in both cases.

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“…It must be analyzed in the context of the many factors related to how epigenetic chemicals work. One must note that these epigenetic food-related chemicals work by different biochemical, signally pathways on different cell types, namely, organ-specific adult stem cells, progenitor cells and terminally differentiated cells [70]. Therefore, while one epigenetic agent (endogenous or exogenous) might inhibit GJIC to be potentially toxic, there will never be "silver bullet" to counter act as a universal dietary chemo-preventive agent.…”

Section: Food Safety Is Dependent On Understanding Food Toxicologymentioning

confidence: 99%

Evolving Concepts of Food Safety: The Need for Understanding Mechanisms of Food Toxicology for Public Policy

2018

ANFS

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Nutrition and diet, which are fundamental to human development and health, in the context of food safety, can be major determinants in the prevention and contributor to both acute and chronic diseases. While the predominant and legitimate concern is to detect and eliminate microbial pathogens that can cause acute illnesses and deaths (estimated 3-5 thousand deaths in the United States and millions of various acute disorders), food components (nutrients, pollutants, additives, processing by-products, etc.) are major factors in chronic diseases (e.g., “metabolic diseases” of diabetes, cardiovascular diseases, cancers). They contribute to millions of long-term health problems and deaths, globally. The objective of this “Communication” is to integrate a shared underlying mechanism of toxicity between acute and chronic diseases. The traditional separation of the strategy to understand “causes” of acute and chronic diseases, while for some practical tactics is understandable (i.e. screening for food-associated pathogens), it fails to recognize that these microbial -associated toxins work by exactly the same molecular/biochemical and cellular mechanisms as the toxicants- causing chronic diseases. Since all chemicals work by mutagenic, cytotoxic or “epigenetic” alteration of gene expression at the transcriptional, translational or post-translational levels, understanding characteristics of all three of these toxicological mechanisms is important so that public policy- strategies for prevention of both these classes of food –related diseases can be made and that a solid foundation for the concept of “functional foods” be made. A moral imperative has to be given to the critical role that safe food can make during pregnancy in preventing long-term health effects later in life.

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Chemopreventive Agents Attenuate Rapid Inhibition of Gap Junctional Intercellular Communication Induced by Environmental Toxicants

Cited by 16 publications

References 43 publications

Improved multiparametric scrape loading-dye transfer assay for a simultaneous high-throughput analysis of gap junctional intercellular communication, cell density and viability

Improved multiparametric scrape loading-dye transfer assay for a simultaneous high-throughput analysis of gap junctional intercellular communication, cell density and viability

Gap Junction Intercellular Communication in the Carcinogenesis Hallmarks: Is This a Phenomenon or Epiphenomenon?

Evolving Concepts of Food Safety: The Need for Understanding Mechanisms of Food Toxicology for Public Policy

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