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Use of retinoic acid/aldehyde dehydrogenase pathway as potential targeted therapy against cancer stem cells
Jan S Moreb1, Deniz A Ucar-Bilyeu2, Abdullah Khan3
1Hematology/Oncology Division, Department of Medicine, University of Florida, 1600 SW Archer Rd, PO Box 100277, Gainesville, FL, 32610, USA. morebsj@medicine.ufl.edu.
Abstract:
A large number of studies have investigated possible drug resistance mechanisms of cancer cells and suggested strategies to overcome it. In this review, we outline the role and function of aldehyde dehydrogenase (ALDH) activity in multiple cellular functions and in cancer stem cells (CSCs) and focus on the role of retinoic acid (RA), one of the products of ALDH isozymes. We discuss our observation that ATRA and other RAs can suppress ALDH activity and decrease different ALDH isozyme proteins and result in detrimental effects on cell proliferation, invasion and chemotherapy sensitivity. We review the known uses of different RAs in the treatment of cancers. We review the use of RAs in combination with chemo-/radiotherapy and the major signaling pathways affected in different tumor types. We provide follow-up on studies that may have used our prior observation with the aim of targeting the CSCs. We conclude with summary of the findings and potential impact of published studies on future use of RAs in the targeting of CSCs and drug resistance.
Insights
Retinoic acids (RAs) can suppress aldehyde dehydrogenase (ALDH) activity, crucial in cancer stem cells (CSCs). This suppression hinders cancer cell proliferation and invasion, offering new strategies to overcome drug resistance.
Area of Science:
- Oncology
- Biochemistry
- Cell Biology
Background:
- Cancer drug resistance is a major clinical challenge.
- Aldehyde dehydrogenase (ALDH) activity is implicated in cancer stem cell (CSC) functions and drug resistance.
- Retinoic acid (RA) is a product of ALDH isozymes and plays a role in cellular regulation.
Purpose of the Study:
- To review the role of ALDH activity in cancer, particularly in CSCs.
- To focus on the function of retinoic acid (RA) in modulating ALDH activity and its implications for cancer.
- To discuss the potential of RAs in overcoming cancer drug resistance.
Main Methods:
- Literature review of studies investigating ALDH activity, CSCs, and RA.
- Analysis of research on the effects of ATRA and other RAs on ALDH activity and protein levels.
- Examination of studies on RA in cancer treatment, alone and in combination therapies.
Main Results:
- Retinoic acids (RAs), including ATRA, can suppress ALDH activity and decrease ALDH isozyme proteins.
- Suppression of ALDH activity by RAs negatively impacts cancer cell proliferation, invasion, and chemotherapy sensitivity.
- RAs show potential in combination with chemo-/radiotherapy, affecting key signaling pathways in various tumor types.
Conclusions:
- Targeting ALDH activity with RAs presents a promising strategy to overcome CSC-mediated drug resistance.
- Further research into RA-based therapies could significantly impact future cancer treatment paradigms.
- Understanding the interplay between ALDH, CSCs, and RAs is crucial for developing effective cancer therapies.
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