Antitumor activity of amidino-substituted benzimidazole and benzimidazo[1,2-<i>a</i>]quinoline derivatives tested in 2D and 3D cell culture systems

Brajša, Karmen; Vujasinović, Ines; Jelić, Dubravko; Trzun, Marija; Zlatar, Ivo; Karminski‐Zamola, Grace; Hranjec, Marijana

doi:10.3109/14756366.2015.1101093

Cited by 28 publications

(23 citation statements)

References 14 publications

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“…Simplistic monolayer cultures have their advantages, but they are often significantly different in gene expression, epigenetics, and cell function compared to native 3D tissues . Also, they often lack cell–cell and cell–matrix interactions, leading to the absence of tissue specific properties. Although animal models are widely used in biomedical research, they fail to faithfully predict human responses in a physiologically relevant manner due to the significant species divergences .…”

Section: Introductionmentioning

confidence: 99%

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

et al. 2019

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The major motivation is to better mimic human physiology and functions at multiscales from the molecular to the cellular, tissue, organ or even whole organism level. Current model systems primarily rely on the monolayer cell cultures and animal models. Simplistic monolayer cultures have their advantages, but they are often significantly different in gene expression, epigenetics, and cell function compared to native 3D tissues. [1,2] Also, they often lack cell-cell and cell-matrix interactions, [2,3] leading to the absence of tissue specific properties. Although animal models are widely used in biomedical research, they fail to faithfully predict human responses in a physiologically relevant manner due to the significant species divergences. [4] The limitations of these systems have provided an impetus for the development of alternative cell-based 3D models in vitro that better resemble the complex functionalities of living organs. Over the last several years, organoids and organ-on-a-chip (OOC), representing the major technological breakthrough, have emerged as two distinct model systems to achieve the same goal of building 3D organotypic models in vitro by bridging the gap between animal models and monolayer cultures. These engineered models are different in terms of cell source, tissue composition, architectural variability, functional features, scales, cellular fidelity, etc. Organoids, primarily evolving from developmental principles, refer to 3D multicellular tissues by self-organization of stem cells or organ-specific progenitors, which can recapitulate the intricate architectures and functionalities of in vivo organs. [5][6][7] Recent breakthroughs in organoid technology have enabled the successful generation of a variety of human organoids, such as the brain, [8,9] intestine, [10,11] liver, [12] kidney, [13,14] lung, [15] etc. These near physiological 3D organoids have garnered momentum for their potential applications in human organ development and disease modeling, drug screening and regenerative medicine. The explosion of organoids research has been catalyzed by the significant progress of stem cell biology and availability of human stem cells. In contrast, the OOC, relying on the bioengineering design principle, is a miniaturized in vitro model that can recreate the functional units of living organs on a microfluidic cell culture device using predifferentiated cells, often cell lines. [1,16] The OOC is primarily evolved from the convergence of tissue engineering and microfabricated technologies, which is characterized by the capability to simulate cellular microenvironment by precise control over fluid flow, mechanical forces and biochemical factors. [4,17] Remarkable progress has been made Significant advances in materials, microscale technology, and stem cell biology have enabled the construction of 3D tissues and organs, which will ultimately lead to more effective diagnostics and therapy. Organoids and organs-on-a-chip (OOC), evolved from developmental biology and bioengineering principles, have e...

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Section: Introductionmentioning

confidence: 99%

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

et al. 2019

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“…As standard drugs we tested doxorubicin, docetaxel, vinorelbine and gemcitabine. All cell lines showed increased chemoresistance in 3D cell growth to standard drugs and for some compounds from our platform we have observed significant disagreement indicating that some prominent compounds can be discarded in the early phase of research, while a chance was given to compounds with false positive result (23). We concluded that, as well as in 2D assay, the shift in IC 50 in a 3D cell culture models is not dependent only on the mode of action of the tested compounds, but it is also affected by the cell line sensitivity and (in case of 3D cultures) spheroid stability, and cell line growth have an impact on the cell line sensitivity.…”

Section: Applications Of 3d Cell Culture In Drug Discoverymentioning

confidence: 92%

Three-dimensional cell cultures as a new tool in drug discovery

et al. 2016

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in 3D format will be shown. Conclusions: Although biological significance of obtained data from 2D and 3D cell cultures is still poorly understood, discrepancy of compunds activity illustrated importance of implementation 3D cell culture assays in early part of drug discovery process.IntroductIon T he costs for successfully introduction a NCE (new chemical entity) drug compound to the market is between $800 million and $1,2 billion, with an average duration of about 10 -15 years. Expenses are even much higher in the case of late stage failure (or failure of already marketed drug) (1). Analyses of clinical trials reveal that about 67% of drug lead molecules fail in late clinical trials stages, most of them due to poor efficacy and safety issues. This high attrition rate indicate that current pre-clinical screening and in vitro models do not adequately provide critical information required for prediction of efficacy and safety issues, which remain the main reasons for drug failure (2). The ability of an assay to produce reliable information about tested NCEs is essential in drug development. Therefore, one way to improve drug dis-

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“…In vivo testing may even be needed to distinguish discrepancies between two separate in vitro study results. In a study regarding the antitumor activity of amidino-substituted benzimidazole and benzimidazo [1, 2-a] quinoline derivatives, the 2D cell cultures used for in vitro testing were found comparable to 3D cell cultures, but significant disagreements in data indicated false positive results, in which in vivo profiling was needed for confirmation [31]. This strengthens the notion that in vitro studies alone, no matter how promising, are not a reliable indicator of a drug's performance which renders the necessity of in vivo studies.…”

Section: The Need For In Vivo Researchmentioning

confidence: 99%

In vivo Studies for Drug Development via Oral Delivery: Challenges, Animal Models and Techniques

Brake¹,

Gumireddy²,

Tiwari³

et al. 2017

Pharm Anal Acta

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Drug discovery and development involves a complex iterative process of new molecules synthesis, formulations, and in vitro analysis, followed by biochemical and cellular assays, with final validation in animal models, and ultimately in humans. The purpose of this article is to present a concise overview of the rationale and challenges for performing in vivo studies, the types of animal models, and modern in vivo research techniques for oral drug delivery.

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Antitumor activity of amidino-substituted benzimidazole and benzimidazo[1,2-a]quinoline derivatives tested in 2D and 3D cell culture systems

Cited by 28 publications

References 14 publications

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

Three-dimensional cell cultures as a new tool in drug discovery

In vivo Studies for Drug Development via Oral Delivery: Challenges, Animal Models and Techniques

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