Evidence map›Paper›PMID 35643815›Full record

ArticleJournal of biomedical optics2022

Inhibition of B-cell lymphoma 2 family proteins alters optical redox ratio, mitochondrial polarization, and cell energetics independent of cell state.

Amani A Gillette, Rebecca A DeStefanis, Stephanie L Pritzl, Dustin A Deming, Melissa C Skala

Open access · goldAbstract read
In one paragraph

Article in Journal of biomedical optics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.8field-weighted citation impact, top 28% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 5 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Amani A GilletteUniversity of Wisconsin, Department of Biomedical Engineering, Madison, Wisconsin, United States.
Rebecca A DeStefanisUniversity of Wisconsin, McArdle Laboratory for Cancer Research, Department of Oncology, Madison, Wi, United States.
Stephanie L PritzlUniversity of Wisconsin, Division of Hematology, Oncology and Palliative Care, Department of Medicin, United States.
Dustin A DemingUniversity of Wisconsin, McArdle Laboratory for Cancer Research, Department of Oncology, Madison, Wi, United States.
Melissa C SkalaUniversity of Wisconsin, Department of Biomedical Engineering, Madison, Wisconsin, United States.
University of Wisconsin–Madison · US

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Christian Capitini · 1985 to 2026
$142.6M
Optical imaging to predict cell-level genetic heterogeneity and treatment sensitivity in colorectal cancerR37CA226526 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI DEMING, DUSTIN A · 2018 to 2024
$4.2M
Optical imaging of pancreas cancer organoids for drug development and personalized treatmentR01CA211082 · NCI · MORGRIDGE INSTITUTE FOR RESEARCH, INC. · PI SKALA, MELISSA CAROLINE · 2017 to 2021
$3.5M
(PQ7) Quantitative in vivo optical imaging of tumor heterogeneityR01CA205101 · NCI · MORGRIDGE INSTITUTE FOR RESEARCH, INC. · PI SKALA, MELISSA CAROLINE · 2016 to 2020
$1.9M
Single Cell Profiling To Define Biomarkers Of Photoreceptor Dysfunction After Gene Editing Within PSC-Derived OrganoidsU01EY032333 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI GAMM, DAVID M, ROY, SUSHMITA · 2020 to 2022
$1.8M
Cellular-level Optical Metabolic Imaging to Predict Drug Response in CancerR01CA185747 · NCI · VANDERBILT UNIVERSITY · PI SKALA, MELISSA CAROLINE · 2014 to 2019
$1.6M
NCI NIH HHS P30 CA014520NCI NIH HHS R01 CA185747NCI NIH HHS R01 CA205101NCI NIH HHS R01 CA211082NCI NIH HHS R37 CA226526NEI NIH HHS U01 EY032333
6 · The paper itself

Abstract

significanceThe optical redox ratio (ORR) [autofluorescence intensity of the reduced form of nicotinamide adenine dinucleotide (phosphate) (NAD(P)H)/flavin adenine dinucleotide (FAD)] provides a label-free method to quantify cellular metabolism. However, it is unclear whether changes in the ORR with B-cell lymphoma 2 (Bcl-2) family protein inhibition are due to metabolic stress alone or compromised cell viability.

aimDetermine whether ABT-263 (navitoclax, Bcl-2 family inhibitor) changes the ORR due to changes in mitochondrial function that are independent of changes in cell viability. APPROACH: SW48 colon cancer cells were used to investigate changes in ORR, mitochondrial membrane potential, oxygen consumption rates, and cell state (cell growth, viability, proliferation, apoptosis, autophagy, and senescence) with ABT-263, TAK-228 [sapanisertib, mammalian target of rapamycin complex 1/2 (mTORC 1/2) inhibitor], and their combination at 24 h.

resultsChanges in the ORR with Bcl-2 inhibition are driven by increases in both NAD(P)H and FAD autofluorescence, corresponding with increased basal metabolic rate and increased mitochondrial polarization. ABT-263 treatment does not change cell viability or induce autophagy but does induce a senescent phenotype. The metabolic changes seen with ABT-263 treatment are mitigated by combination with mTORC1/2 inhibition.

conclusionsThe ORR is sensitive to increases in mitochondrial polarization, energetic state, and cell senescence, which can change independently from cell viability.

Indexed as

Flavin-Adenine DinucleotideNADMitochondriaOxidation-ReductionProto-Oncogene Proteins c-bcl-2Flavin-Adenine DinucleotideNADProto-Oncogene Proteins c-bcl-2autofluorescenceflavin adenine dinucleotidemitochondrianicotinamide adenine dinucleotide hydrogenoptical redox ratio

Identifiers

PMID35643815
PMCPMC9142839
OpenAlexW4281761004

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.