Evidence mapPaperPMID 34869321Full record

ArticleFrontiers in cell and developmental biology2021

Repurposing Combination Therapy of Voacamine With Vincristine for Downregulation of Hypoxia-Inducible Factor-1α/Fatty Acid Synthase Co-axis and Prolyl Hydroxylase-2 Activation in ER+ Mammary Neoplasia.

Lakhveer Singh, Subhadeep Roy, Anurag Kumar, Shubham Rastogi, Dinesh Kumar, Mohd Nazam Ansari, Abdulaziz S Saeedan, Manjari Singh, Gaurav Kaithwas

Open access · goldAbstract read
In one paragraph

Article in Frontiers in cell and developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.9field-weighted citation impact, top 31% 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

6 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Regulation of Transactivation at C-TAD Domain of HIF-1Oxidative medicine and cellular longevity · 2022
    Review
  6. Article
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

9 authors at 4 institutions in 2 countries.

Lakhveer SinghDepartment of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, India.
Subhadeep RoyDepartment of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, India.
Anurag KumarDepartment of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, India.
Shubham RastogiDepartment of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, India.
Dinesh KumarCenter for Biomedical Research, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Mohd Nazam AnsariDepartment of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.
Abdulaziz S SaeedanDepartment of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.
Manjari SinghDepartment of Pharmaceutical Sciences, Assam University, Silchar, India.
Gaurav KaithwasDepartment of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, India.
Babasaheb Bhimrao Ambedkar University · INPrince Sattam Bin Abdulaziz University · SAAssam University · INSanjay Gandhi Post Graduate Institute of Medical Sciences · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The current study investigated the role of combination therapy with voacamine and vincristine in preventing mammary gland carcinoma through prolyl hydroxylase-2 activation. Prolyl hydroxylase-2 activation leads to the downregulation of hypoxia-inducible factor-1α and fatty acid synthase. Overexpression of hypoxia-inducible factor-1α and fatty acid synthase has been previously reported in solid tumors of the mammary gland. After screening a battery of natural compounds similar to vincristine, voacamine was selected as a possible prolyl hydroxylase-2 activator, and its activity was evaluated using a 7,12-dimethylbenz[a]anthracene-induced rat model. The combination therapy was evaluated for cardiac toxicity using a hemodynamic profile. Angiogenic markers were evaluated by carmine staining. Monotherapy and combination therapy were also evaluated for liver and kidney toxicity using hematoxylin and eosin staining. The antioxidant potential was delineated using oxidative stress markers. The serum metabolomic profile was studied using NMR spectroscopy, and the disruption of fatty acids was evaluated using gas chromatography. Western blotting of proteins involved in hypoxic pathways was performed to decipher the action of therapy at the molecular level. Immunoblotting analysis validated that combination therapy has potential toss with prolyl hydroxylase-2 activity and thus initiates proteolytic degradation of hypoxia-inducible factor-1α and its consequent effects. Combination therapy also stimulated programmed cell death (apoptosis) in rapidly dividing cancer cells. The present study explored the role of voacamine inactivation of prolyl hydroxylase-2, which can decrease the overexpression of hypoxia-inducible factor-1α and fatty acid synthase in mammary gland carcinoma cells.

Indexed as

fatty acid synthase (FASN)hypoxia inducible factor-1α (HIF-1α)mammary gland carcinomaprolyl hydroxylase-2repurposable drugsvoacamine

Identifiers

PMID34869321
PMCPMC8637442
OpenAlexW3212226199

What Socratic holds

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Registered trials

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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 Socratic graph.