Evidence map›Paper›PMID 31645574›Full record

ArticleScientific reports2019

Mithramycin A Inhibits Colorectal Cancer Growth by Targeting Cancer Stem Cells.

Waise Quarni, Rinku Dutta, Ryan Green, Sandhyabanu Katiri, Bhaumik Patel, Shyam S Mohapatra, Subhra Mohapatra

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
3.4field-weighted citation impact, top 6% 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

42 citing papers in PubMed, 63 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

7 authors at 2 institutions in 1 country.

Waise QuarniDepartment of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA.
Rinku DuttaDepartment of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA.
Ryan GreenDepartment of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA.
Sandhyabanu KatiriDepartment of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA.
Bhaumik PatelHunter Holmes McGuire VA Medical Center, Richmond, VA, 23249, USA.
Shyam S MohapatraDepartment of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA. smohapat@health.usf.edu.
Subhra MohapatraDepartment of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA. smohapa2@health.usf.edu.ORCID http://orcid.org/0000-0001-7636-0174
University of South Florida · USVirginia Commonwealth University · US

Funding

BLRD VA I01 BX003413BLRD VA IK6 BX003778BLRD VA IK6 BX004212
6 · The paper itself

Abstract

The pivotal role of cancer initiating stem cells (CSCs) in tumor initiation, growth, metastasis and drug resistance has led to the postulation of a 'total cancer therapy' paradigm, which involves targeting both cancer cells and CSCs for effective therapy. However, the progress in identifying drugs for total cancer therapy has been limited. Herein, we show for the first time that mithramycin A (Mit-A) can successfully inhibit CSC proliferation, in addition to inhibiting bulk cancer cells in a model of colorectal cancer (CRC), the second leading cause of death among men and women in the United States. To this end, a polymeric nanofiber scaffold culture system was established to develop 3D tumor organoids (tumoroids) from CRC cell lines such as HT29, HCT116, KM12, CT26 and MC38 as well as ex vivo mouse tumors. These tumoroids possessed increased expression of CSC markers and transcription factors, expanded the number of CSCs in culture and increased CSC functional properties measured by aldehyde dehydrogenase activity. Screening of an NCI library of FDA approved drugs led to the identification of Mit-A as a potential total cancer therapy drug. In both sphere and tumoroid culture, Mit-A inhibits cancer growth by reducing the expression of cancer stemness markers. In addition, Mit-A inhibits the expression of SP1, a previously known target in CRCs. Moreover, Mit-A significantly reduces growth of tumoroids in ex vivo cultures and CRC tumor growth in vivo. Finally, a dose-dependent treatment on CRC cells indicate that Mit-A significantly induces the cell death and PARP-cleavage of both CSC and non-CSC cells. Taken together the results of these in vitro, ex vivo and in vivo studies lead to the inference that Mit-A is a promising drug candidate for total cancer therapy of CRCs.

Indexed as

AnimalsAntineoplastic AgentsCell Line, TumorCell ProliferationColorectal NeoplasmsHCT116 CellsHT29 CellsHumansMice, Inbred C57BLNeoplastic Stem CellsPlicamycinAntineoplastic Agentsmithramycin APlicamycin

Identifiers

PMID31645574
PMCPMC6811578
OpenAlexW2982081204

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.