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Cited by 35Optical Imaging and Spectroscopy TechniquesSpectroscopy Techniques in Biomedical and Chemical ResearchCell Image Analysis Techniques

Phenotypic profiling of Raf inhibitors and mitochondrial toxicity in 3D tissue using biodynamic imaging

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An, Ran, Merrill, Dan, Avramova, Larisa, Sturgis, Jennifer, Tsiper, Maria, Robinson, J. Paul, Turek, John, Nolte, David D.·2014·SLAS Discovery
DOI 10.1177/1087057113516674PMC PMC4028716
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Abstract

The existence of phenotypic differences in the drug responses of 3D tissue relative to 2D cell culture is a concern in high-content drug screening. Biodynamic imaging is an emerging technology that probes 3D tissue using short-coherence dynamic light scattering to measure the intracellular motions inside tissues in their natural microenvironments. The information content of biodynamic imaging is displayed through tissue dynamics spectroscopy (TDS) but has not previously been correlated against morphological image analysis of 2D cell culture. In this article, a set of mitochondria-affecting compounds (FCCP, valinomycin, nicardipine, ionomycin) and Raf kinase inhibitors (PLX4032, PLX4720, GDC, and sorafenib) are applied to multicellular tumor spheroids from two colon adenocarcinoma cell lines (HT-29 and DLD-1). These were screened by TDS and then compared against conventional image-based high-content analysis (HCA). The responses to the Raf inhibitors PLX4032 and PLX4720 are grouped separately by cell line, reflecting the Braf/Kras difference in these cell lines. There is a correlation between TDS and HCA phenotypic clustering for most cases, which demonstrates the ability of dynamic measurements to capture phenotypic responses to drugs. However, there are significant 2D versus 3D phenotypic differences exhibited by several of the drugs/cell lines.

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  • Advanced spectroscopic techniques have been employed to capture spatial and compositional changes associated with treatment response.

    “Beyond these biochemical assays, efforts have been made to employ advanced spectroscopic techniques to capture spatial and compositional changes associated with treatment response [311,312,313].”

    From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [311]

    The Introduction: Tissue Dynamics Spectroscopy (page unavailable) says motility contrast imaging provides spatial maps of tissue responses to drugs, while tissue dynamics spectroscopy provides drug-response spectrograms. The paper supports the use of spectroscopic imaging to capture spatial and dynamic treatment responses, but the cited passages do not show it measuring compositional changes. (LLM, conf=0.84)

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References 37 · Cited by 35

Research works printed but not linked: 31

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Authors
An, R., Merrill, D., Avramova, L., Sturgis, J., Tsiper, M., Robinson, J. P., Turek, J., & Nolte, D. D.
Affiliations
  • Purdue University West Lafayette (US)
  • Purdue Global (US)
Corresponding author
Nolte, David D.
ORCID
Venue
SLAS Discovery
Publisher
Elsevier BV
Published
2014-04
Volume
19
Issue
4
Pages
526-537
ISSN
2472-5552 (ISSN-L)
DOI
10.1177/1087057113516674
PMC
PMC4028716
OpenAlex
W2139799760
Cited by
35
References
37
Citations by year
2025: 3 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 2 · 2016: 2 · 2015: 8 · 2014: 2
FWCI
3.10
Type
journal article
Language
en
Open access
Licence
Locations
  • SLAS DISCOVERY (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Eli Lilly and Company
  • Purdue University
  • National Institutes of Health
  • National Institute of Biomedical Imaging and Bioengineering (R01EB016582)
  • Division of Chemical, Bioengineering, Environmental, and Transport Systems
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Spectroscopy Techniques in Biomedical and Chemical Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Cell Image Analysis Techniques
Keywords
Raf kinase inhibitor, mitochondrial toxicity, tumor spheroids, colon adenocarcinoma, HT-29 cells, DLD-1 cells, vemurafenib, PLX4720, sorafenib, FCCP, valinomycin, nicardipine, ionomycin, high-content drug screening
MeSH terms
Drug Evaluation, Preclinical, Drug Screening Assays, Antitumor, Humans, Mitochondria, Spectrophotometry, Tumor Cells, Cultured, Cluster Analysis, Spheroids, Cellular, Cell Line, Tumor, Protein Kinase Inhibitors, Proto-Oncogene Proteins B-raf, Drug Discovery, High-Throughput Screening Assays

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