Isotretinoin and thalidomide down-regulate c-MYC gene expression and modify proteins associated with cancer in hepatic cells

Patricia Nefertari Ramírez-flores, Paulina J. Barraza-reyna, Alain Aguirre-vázquez, María E. Camacho-moll, Carlos Enrique Guerrero-beltrán, Diana Resendez-pérez, Vianey González-villasana, Jesús Norberto Garza-gonzález, Beatriz Silva-ramírez, Fabiola Castorena-torres, Mario Bermúdez de León

Resultado de la investigaciónrevisión exhaustiva

Resumen

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.
Idioma originalEnglish
Número de artículo5742
PublicaciónMolecules
Volumen26
N.º19
DOI
EstadoPublished - 1 oct. 2021

Nota bibliográfica

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Química analítica
  • Química (miscelánea)
  • Medicina molecular
  • Ciencias farmacéuticas
  • Descubrimiento de medicamentos
  • Química física y teórica
  • Química orgánica

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