Targeting the retinoic acid pathway to eradicate cancer stem cells

Geoff Brown*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

All-trans retinoic acid is a morphogen during embryogenesis and a teratogen. Cancer is an error of development, and the retinoic acid receptors (RAR) for all-trans retinoic acid play a role in cancer. Expression of the cytosolic aldehyde dehydrogenases, which mediate the last step to the synthesis of all-trans retinoic acid, is deregulated in various human cancers. Inhibiting these enzymes using a variety of agents reduced the proliferation of lung cancer cells, reduced the proliferation and induced apoptosis of ovarian, prostate, squamous, and uterine cancer cells, and sensitised breast, colorectal and ovarian cancer cells to chemotherapeutic agents. RARγ is an oncogene within some cases of AML, cholangiocarcinoma, colorectal cancer, clear cell renal cell carcinoma, hepatocellular carcinoma, pancreatic ductal adenocarcinoma, prostate cancer, and ovarian cancer. Pan-RAR and RARγ antagonist inhibition of the action of RARγ led to necroptosis of human prostate and pediatric brain tumour cancer stem cells. Treatment of hepatocellular carcinoma cells with the flavenoid acacetin, which interferes with the action of RARγ, decreased cell growth and induced apoptosis. Targeting the retinoic acid pathway is promising regarding the development of new drugs to eradicate cancer stem cells.
Original languageEnglish
Article number2373
Number of pages19
JournalInternational Journal of Molecular Sciences
Volume24
Issue number3
DOIs
Publication statusPublished - 25 Jan 2023

Bibliographical note

This article belongs to the Special Issue Stem Cell Biology and Cancer

Keywords

  • all‐trans retinoic acid
  • carcinomas
  • cancer stem cells
  • oncogenes
  • retinoic acid receptor γ
  • all-trans retinoic acid
  • Review

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