Evidence map›Paper›PMID 34209047›Full record

ArticleCancers2021

Natural Merosesquiterpenes Activate the DNA Damage Response via DNA Strand Break Formation and Trigger Apoptotic Cell Death in p53-Wild-type and Mutant Colorectal Cancer.

Apisada Jiso, Philipp Demuth, Madeleine Bachowsky, Manuel Haas, Nina Seiwert, Daniel Heylmann, Birgit Rasenberger, Markus Christmann, Lea Dietrich, Thomas Brunner and 4 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. 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
1.7field-weighted citation impact, top 17% 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, 15 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
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

14 authors at 5 institutions in 3 countries.

Apisada JisoDivision of Food Chemistry and Toxicology, Department of Chemistry, Technical University of Kaiserslautern, 67663 Kaiserslautern, Germany.ORCID 0000-0002-4297-7819
Philipp DemuthDivision of Food Chemistry and Toxicology, Department of Chemistry, Technical University of Kaiserslautern, 67663 Kaiserslautern, Germany.
Madeleine BachowskyDivision of Food Chemistry and Toxicology, Department of Chemistry, Technical University of Kaiserslautern, 67663 Kaiserslautern, Germany.
Manuel HaasDivision of Food Chemistry and Toxicology, Department of Chemistry, Technical University of Kaiserslautern, 67663 Kaiserslautern, Germany.
Nina SeiwertDivision of Food Chemistry and Toxicology, Department of Chemistry, Technical University of Kaiserslautern, 67663 Kaiserslautern, Germany.
Daniel HeylmannRudolf Buchheim Institute of Pharmacology, Justus Liebig University Giessen, 35392 Giessen, Germany.
Birgit RasenbergerInstitute of Toxicology, University Medical Center Mainz, 55131 Mainz, Germany.
Markus ChristmannInstitute of Toxicology, University Medical Center Mainz, 55131 Mainz, Germany.ORCID 0000-0002-9672-231X
Lea DietrichBiochemical Pharmacology, Department of Biology, University of Konstanz, 78464 Konstanz, Germany.ORCID 0000-0002-5931-7964
Thomas BrunnerBiochemical Pharmacology, Department of Biology, University of Konstanz, 78464 Konstanz, Germany.
RiyantiInstitute for Insect Biotechnology, Justus-Liebig-University Giessen, 35392 Giessen, Germany.ORCID 0000-0003-0665-8092
Till F SchäberleInstitute for Insect Biotechnology, Justus-Liebig-University Giessen, 35392 Giessen, Germany.ORCID 0000-0001-9947-8079
Anuchit PlubrukarnDepartment of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, Songkhla 90112, Thailand.ORCID 0000-0002-2340-7220
Jörg FahrerDivision of Food Chemistry and Toxicology, Department of Chemistry, Technical University of Kaiserslautern, 67663 Kaiserslautern, Germany.ORCID 0000-0001-5225-2718
University of Kaiserslautern · DEJustus-Liebig-Universität Gießen · DEJohannes Gutenberg University Mainz · DEPrince of Songkla University · THUniversity of Konstanz · DE

Funding

Bundesministerium für Bildung und Forschung 01DP17037Indonesia Endowment Fund for Education 20160222305487Royal Golden Jubilee (RGJ) Ph.D. Programme PHD/0094/2556Wilhelm Sander-Stiftung 2016.039.2
6 · The paper itself

Abstract

Colorectal cancer (CRC) is a frequently occurring malignant disease with still low survival rates, highlighting the need for novel therapeutics. Merosesquiterpenes are secondary metabolites from marine sponges, which might be useful as antitumor agents. To address this issue, we made use of a compound library comprising 11 isolated merosesquiterpenes. The most cytotoxic compounds were smenospongine > ilimaquinone ≈ dactylospontriol, as shown in different human CRC cell lines. Alkaline Comet assays and γH2AX immunofluorescence microscopy demonstrated DNA strand break formation in CRC cells. Western blot analysis revealed an activation of the DNA damage response with CHK1 phosphorylation, stabilization of p53 and p21, which occurred both in CRC cells with p53 knockout and in p53-mutated CRC cells. This resulted in cell cycle arrest followed by a strong increase in the subG1 population, indicative of apoptosis, and typical morphological alterations. In consistency, cell death measurements showed apoptosis following exposure to merosesquiterpenes. Gene expression studies and analysis of caspase cleavage revealed mitochondrial apoptosis via

Indexed as

apoptosischemotherapycolorectal cancerDNA damagenatural compoundstumor suppressor p53

Identifiers

PMID34209047
PMCPMC8268692
OpenAlexW3175924201

What OpenQuestion holds

Textmetadata
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.