Related Experiment Video

Updated: Sep 2, 2025

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

1.5K

Dolutegravir Inhibits Proliferation and Motility of BT-20 Tumor Cells Through Inhibition of Human Endogenous

Jiayi Li1, John Lin1, John R Lin1

  • 1Medical School, Liberty University College of Osteopathic Medicine, Lynchburg, USA.

Cureus
|August 8, 2022
PubMed

Insights

Antiretroviral drugs like dolutegravir show promise in cancer treatment by inhibiting endogenous retroviruses (ERVs). This study found dolutegravir suppressed cancer cell proliferation linked to human endogenous retrovirus K (HERV-K) but unexpectedly promoted metastasis in some models.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • Endogenous retroviruses (ERVs) are increasingly implicated in cancer cell proliferation.
  • Repurposing antiretroviral agents offers a novel strategy for cancer therapy targeting ERVs.

Purpose of the Study:

  • To investigate the potential of antiretroviral agents to inhibit ERVs for cancer treatment.
  • To explore dolutegravir (DTG) as an inhibitor of ERVs and its antiproliferative effects on cancer cells.

Main Methods:

  • Screened antiretroviral agents for ERV inhibition and antiproliferative activity.
  • Utilized cancer cell lines (BT-20, 4T1) to study DTG's effects on ERV expression (HERV-K, MMTV).
  • Assessed DTG's in vitro mechanisms, including effects on cell motility, invasiveness, and gene expression (E-cadherin).

Main Results:

  • Dolutegravir (DTG) inhibited proliferation of multiple cancer cell lines, with potency correlated to human endogenous retrovirus K (HERV-K) expression.
  • DTG suppressed HERV-K and mouse mammary tumor virus (MMTV) expression in vitro.
  • Overexpression or knockdown of HERV-K modulated DTG resistance.
  • DTG enhanced E-cadherin expression and reduced cell motility/invasiveness in vitro.
  • Unexpectedly, DTG promoted MMTV env gene expression and metastasis in vivo.

Conclusions:

  • Endogenous retroviruses play a role in tumor development.
  • Antiretroviral agents like DTG show potential for cancer treatment by targeting ERVs.
  • Further research into antiretroviral agents for ERV-active malignancies is warranted, considering potential differential in vivo effects.
Keywords:
4t1 cellsanti-cancer therapyantiretroviral agentbreast cancerbt-20 cellsdolutegravirendogenous retrovirusesherv-kmetastasismouse mammary tumor virus

More Related Videos

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors05:46

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors

Published on: April 9, 2014

17.9K
A High-throughput Cre-Lox Activated Viral Membrane Fusion Assay to Identify Inhibitors of HIV-1 Viral Membrane Fusion07:22

A High-throughput Cre-Lox Activated Viral Membrane Fusion Assay to Identify Inhibitors of HIV-1 Viral Membrane Fusion

Published on: August 14, 2018

6.5K

Related Concept Videos

Retrovirus Life Cycles01:10

Retrovirus Life Cycles

Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
46.6K
Retroviruses02:33

Retroviruses

Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
12.6K
Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
5.2K
Non-LTR Retrotransposons03:18

Non-LTR Retrotransposons

As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
11.8K