Medical Significance of Uterine Corpus Endometrial Carcinoma Patients Infected With SARS-CoV-2 and Pharmacological Characteristics of Plumbagin

Front Endocrinol (Lausanne). 2021 Oct 12:12:714909. doi: 10.3389/fendo.2021.714909. eCollection 2021.

Abstract

Background: Clinically, evidence shows that uterine corpus endometrial carcinoma (UCEC) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have a higher death-rate. However, current anti-UCEC/coronavirus disease 2019 (COVID-19) treatment is lacking. Plumbagin (PLB), a pharmacologically active alkaloid, is an emerging anti-cancer inhibitor. Accordingly, the current report was designed to identify and characterize the anti-UCEC function and mechanism of PLB in the treatment of patients infected with SARS-CoV-2 via integrated in silico analysis.

Methods: The clinical analyses of UCEC and COVID-19 in patients were conducted using online-accessible tools. Meanwhile, in silico methods including network pharmacology and biological molecular docking aimed to screen and characterize the anti-UCEC/COVID-19 functions, bio targets, and mechanisms of the action of PLB.

Results: The bioinformatics data uncovered the clinical characteristics of UCEC patients infected with SARS-CoV-2, including specific genes, health risk, survival rate, and prognostic index. Network pharmacology findings disclosed that PLB-exerted anti-UCEC/COVID-19 effects were achieved through anti-proliferation, inducing cytotoxicity and apoptosis, anti-inflammation, immunomodulation, and modulation of some of the key molecular pathways associated with anti-inflammatory and immunomodulating actions. Following molecular docking analysis, in silico investigation helped identify the anti-UCEC/COVID-19 pharmacological bio targets of PLB, including mitogen-activated protein kinase 3 (MAPK3), tumor necrosis factor (TNF), and urokinase-type plasminogen activator (PLAU).

Conclusions: Based on the present bioinformatic and in silico findings, the clinical characterization of UCEC/COVID-19 patients was revealed. The candidate, core bio targets, and molecular pathways of PLB action in the potential treatment of UCEC/COVID-19 were identified accordingly.

Keywords: cancer; clinical; mechanism and characterization; pharmacologic (drug) therapy; target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • COVID-19 Drug Treatment*
  • COVID-19* / complications
  • COVID-19* / diagnosis
  • COVID-19* / genetics
  • Calcium-Binding Proteins / drug effects
  • Calcium-Binding Proteins / metabolism
  • Carcinoma, Endometrioid* / complications
  • Carcinoma, Endometrioid* / diagnosis
  • Carcinoma, Endometrioid* / drug therapy
  • Carcinoma, Endometrioid* / genetics
  • Computational Biology
  • Drug Screening Assays, Antitumor / methods
  • Endometrial Neoplasms* / complications
  • Endometrial Neoplasms* / diagnosis
  • Endometrial Neoplasms* / drug therapy
  • Endometrial Neoplasms* / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Regulatory Networks / drug effects
  • Genetic Association Studies
  • Host-Pathogen Interactions* / drug effects
  • Host-Pathogen Interactions* / genetics
  • Humans
  • Membrane Proteins / drug effects
  • Membrane Proteins / metabolism
  • Middle Aged
  • Mitogen-Activated Protein Kinase 3 / drug effects
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Molecular Docking Simulation / methods
  • Naphthoquinones / pharmacology*
  • Naphthoquinones / therapeutic use
  • Prognosis
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / metabolism
  • Uterus / drug effects
  • Uterus / metabolism
  • Uterus / pathology
  • Uterus / virology

Substances

  • Calcium-Binding Proteins
  • Membrane Proteins
  • Naphthoquinones
  • PLAU protein, human
  • Tumor Necrosis Factor-alpha
  • phospholamban
  • MAPK3 protein, human
  • Mitogen-Activated Protein Kinase 3
  • plumbagin