Evidence map›Paper›PMID 37568755›Full record

ArticleCancers2023

Therapeutic Potential of Targeting the Cytochrome P450 Enzymes Using Lopinavir/Ritonavir in Colorectal Cancer: A Study in Monolayers, Spheroids and In Vivo Models.

Maryam Alaei, Seyedeh Elnaz Nazari, Ghazaleh Pourali, AliReza Asadnia, Mehrdad Moetamani-Ahmadi, Hamid Fiuji, Hamid Tanzadehpanah, Fereshteh Asgharzadeh, Fatemeh Babaei, Fatemeh Khojasteh-Leylakoohi and 8 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Cancers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.0field-weighted citation impact, top 15% 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, 8 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 6 institutions in 6 countries.

Maryam AlaeiDepartment of Clinical Biochemistry, Mashhad University of Medical Sciences, Mashhad 13944-91388, Iran.
Seyedeh Elnaz NazariMetabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad 13944-91388, Iran.
Ghazaleh PouraliMetabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad 13944-91388, Iran.
AliReza AsadniaMetabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad 13944-91388, Iran.
Mehrdad Moetamani-AhmadiMetabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad 13944-91388, Iran.ORCID 0009-0001-5475-4997
Hamid FiujiBasic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad 13944-91388, Iran.
Hamid TanzadehpanahMetabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad 13944-91388, Iran.
Fereshteh AsgharzadehMetabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad 13944-91388, Iran.ORCID 0000-0002-8349-3722
Fatemeh BabaeiMetabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad 13944-91388, Iran.
Fatemeh Khojasteh-LeylakoohiMetabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad 13944-91388, Iran.
Ibrahim Saeed GataaCollege of Medicine, University of Warith Al-Anbiyaa, Karbala 56001, Iraq.
Mohammad Ali KianiBasic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad 13944-91388, Iran.
Gordon A FernsDepartment of Medical Education, Brighton & Sussex Medical School, Falmer, Brighton, Sussex BN1 9PH, UK.
Alfred King-Yin LamPathology, School of Medicine and Dentistry, Gold Coast Campus, Griffith University, Gold Coast, QLD 4222, Australia.ORCID 0000-0003-2771-564X
Seyed Mahdi HassanianDepartment of Clinical Biochemistry, Mashhad University of Medical Sciences, Mashhad 13944-91388, Iran.
Majid KhazaeiMetabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad 13944-91388, Iran.
Elisa GiovannettiDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam U.M.C., VU. University Medical Center (VUMC), 1081 HV Amsterdam, The Netherlands.ORCID 0000-0002-7565-7504
Amir AvanMetabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad 13944-91388, Iran.ORCID 0000-0002-4968-0962
Mashhad University of Medical Sciences · IRBrighton and Sussex Medical School · GBFondazione Pisa · ITGriffith University · AUQueensland University of Technology · AUUniversity of Kerbala · IQ

Funding

Mashhad University of Medical Sciences 4011318
6 · The paper itself

Abstract

Cytochrome P450 (CYP450) enzyme has been shown to be expressed in colorectal cancer (CRC) and its dysregulation is linked to tumor progression and a poor prognosis. Here we investigated the therapeutic potential of targeting CYP450 using lopinavir/ritonavir in CRC. The integrative systems biology method and RNAseq were utilized to investigate the differential levels of genes associated with patients with colorectal cancer. The antiproliferative activity of lopinavir/ritonavir was evaluated in both monolayer and 3-dimensional (3D) models, followed by wound-healing assays. The effectiveness of targeting CYP450 was examined in a mouse model, followed by histopathological analysis, biochemical tests (MDA, SOD, thiol, and CAT), and RT-PCR. The data of dysregulation expressed genes (DEG) revealed 1268 upregulated and 1074 down-regulated genes in CRC. Among the top-score genes and dysregulated pathways, CYPs were detected and associated with poor prognosis of patients with CRC. Inhibition of CYP450 reduced cell proliferation via modulating survivin, Chop, CYP13a, and induction of cell death, as detected by AnnexinV/PI staining. This agent suppressed the migratory behaviors of cells by induction of E-cadherin. Moreover, lopinavir/ritonavir suppressed tumor growth and fibrosis, which correlated with a reduction in SOD/thiol levels and increased MDA levels. Our findings illustrated the therapeutic potential of targeting the CYP450 using lopinavir/ritonavir in colorectal cancer, supporting future investigations on this novel therapeutic approach for the treatment of CRC.

Indexed as

colorectal cancercytochrome P450lopinavir/ritonavirtumor growth

Identifiers

PMID37568755
PMCPMC10417395
OpenAlexW4385498154

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.