Synergistic effect of co-treatment with all-trans retinoic acid and 9-cis retinoic acid on human lung cancer cell line at molecular level
Open accessAbstract
The major challenge in treating cancers with ATRA is the limited availability inside the cell and resistance developed in prolonged treatment. We made an attempt for co-treatment of human NSCLC cell lines (A549) with ATRA and its isomeric precursor (9 cis RA). In this study, the growth inhibitory effect of ATRA, 9 cis RA and combination of both were tested in A549 cells by MTT and Trypan blue assays. As the effects of retinoid are mediated through their receptors, their gene expression levels were analyzed by RT-PCR. The target gene receptor, RAR-β protein expression, was analyzed by immunocytochemistry. The cancer cell (A549) growth inhibitory effect was significantly (p ≤ 0.001) enhanced in combination treatment when compared with the result of individual treatments. The mRNA expression levels of both RAR-β and RXR-β were found to be increased in co-treatment (band density of 0.75 and 0.806, respectively) when compared with 9 cis RA treatment (0.25 and 0.112) and ATRA treatment (0.01 and 0.081). A concomitant enhancement in the target RAR-β protein expression was observed in co-treated cells when compared with individual treatments. We thus conclude that the co-treatment had increased the availability of ATRA, by isomerization of the 9 cis RA which then resulted in an increased expression of both RAR-β and RXR-β receptors and the target protein RAR-β which in turn inhibited lung cancer cell growth. Our study results have explored the mechanism of synergistic effect of co-treatment with ATRA and 9 cis RA and further preclinical studies are necessary to validate the application of co-treatment of retinoid in clinical use.
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ATRA has been reported to inhibit the proliferation of lymphoma and lung, liver and solid ovarian tumors.
“In addition to its differentiating effect, it has also been reported to inhibit the proliferation of lymphoma and lung, liver and solid ovarian tumors [7,185,193].”
From Vitamin A Update: Forms, Sources, Kinetics, Detection, Function, Deficiency, Therapeutic Use and Toxicity (2021) · cites this paper as [193]
The Growth inhibitory activity of retinoid by MTT assay section (page not provided) reports reduced viability in lung cancer A549 cells treated with ATRA alone. The paper does not report ATRA inhibiting proliferation of lymphoma, liver tumors, or solid ovarian tumors; its lung-cancer finding is also limited to a cell line, not tumors generally. (LLM, conf=0.90)
Experimental — accuracy not yet measuredRetinoids have been successfully used in treating cancer.
“Apart from the well-known indications in hypovitaminosis and skin diseases, retinoids have been successfully used in treating cancer”
From Vitamin A Update: Forms, Sources, Kinetics, Detection, Function, Deficiency, Therapeutic Use and Toxicity (2021) · cites this paper as [193]
Developing resistance to ATRA treatment by tumors is common.
“Importantly, developing resistance to ATRA treatment by tumors is common”
From Vitamin A Update: Forms, Sources, Kinetics, Detection, Function, Deficiency, Therapeutic Use and Toxicity (2021) · cites this paper as [193]
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- Authors
- Bama, E. S., Grace, V. M. B., Sundaram, V., & Jesubatham, P. D.
- Affiliations
- Karunya University (IN)
- Corresponding author
- Grace, V. M. Berlin
- ORCID
- Grace, V. M. Berlin
- Venue
- 3 Biotech
- Published
- 2019-03-30
- Volume
- 9
- Issue
- 4
- Pages
- 159-159
- ISSN
- 2190-572X (ISSN-L)
- 2190-5738
- PMC
- PMC6441431
- OpenAlex
- W2931009117
- Cited by
- 8
- References
- 28
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 1
- FWCI
- 0.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- 3 Biotech (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Karunya Short Term Project Grant - Karunya Institute of Technology and Science (REG/IQ/O/4264)
- Department of Science and Technology - Science and Engineering Research Board, Government of India (SB/YS/LS-252/2013)
- Department of Biotechnology (BT/PR14632/NNT/28/824/2015)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- all-trans retinoic acid, 9-cis-retinoic acid, synergistic drug combination, non-small cell lung cancer, A549 cells, RARβ, retinoid receptors, cell growth inhibition, retinoid resistance
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