Hepatocellular carcinoma (HCC) is the most common form of liver cancer. The number of cases is increasing and the trend for the next few years is not encouraging. HCC is usually detected in the advanced stages of the disease, and pharmacological therapies are not entirely effective. For this reason, it is necessary to search for new therapeutic options. The objective of this work was to evaluate the effect of the drugs isotretinoin and thalidomide on c-MYC expression and cancer-related proteins in an HCC cellular model. The expression of c-MYC was measured using RTqPCR and western blot assays. In addition, luciferase activity assays were performed for the c-MYC promoters P1 and P2 using recombinant plasmids. Dose-response-time analyses were performed for isotretinoin or thalidomide in cells transfected with the c-MYC promoters. Finally, a proteome profile analysis of cells exposed to these two drugs was performed and the results were validated by western blot. We demonstrated that in HepG2 cells, isotretinoin and thalidomide reduced c-MYC mRNA expression levels, but this decrease in expression was linked to the regulation of P1 and P1- P2 c-MYC promoter activity in isotretinoin only. Thalidomide did not exert any effect on c-MYC promoters. Also, isotretinoin and thalidomide were capable of inducing and repressing proteins associated with cancer. In conclusion, isotretinoin and thalidomide down-regulate c-MYC mRNA expression and this is partially due to P1 or P2 promoter activity, suggesting that these drugs could be promising options for modulating the expression of oncogenes and tumor suppressor genes in HCC.
Bibliographical noteFunding Information:
This research was funded by Instituto Mexicano del Seguro Social, grant number FIS/IMSS/PROT/G17-2/1746 and the APC was funded by Tecnologico de Monterrey.Authors thank Israel R. Benavides Páramo for his administrative support, and Biol. Jesús Pablo Gómez Islas for his technical advice. We thank Michael Cole from Norris Cotton Cancer Center, New Hampshire, USA for his generous gift of c-MYC plasmids. P.N.R.-F. and A.A.- V. were recipients of CONACyT and IMSS scholarships, and P.J.B.-R. was recipient of CONACyT scholarship for graduate program.
Funding: This research was funded by Instituto Mexicano del Seguro Social, grant number FIS/IMSS/PROT/G17‐2/1746 and the APC was funded by Tecnologico de Monterrey.
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All Science Journal Classification (ASJC) codes
- Analytical Chemistry
- Chemistry (miscellaneous)
- Molecular Medicine
- Pharmaceutical Science
- Drug Discovery
- Physical and Theoretical Chemistry
- Organic Chemistry