Isotretinoin and Thalidomide Down-Regulate <i>c-MYC</i> 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
Affiliations
Patricia Nefertari Ramírez-Flores
Centro de Investigación Biomédica del Noreste, Departamento de Biología Molecular, Instituto Mexicano del Seguro Social, Monterrey 64720, Mexico
Paulina J. Barraza-Reyna
Centro de Investigación Biomédica del Noreste, Departamento de Biología Molecular, Instituto Mexicano del Seguro Social, Monterrey 64720, Mexico
Alain Aguirre-Vázquez
Centro de Investigación Biomédica del Noreste, Departamento de Biología Molecular, Instituto Mexicano del Seguro Social, Monterrey 64720, Mexico
María E. Camacho-Moll
Centro de Investigación Biomédica del Noreste, Departamento de Biología Molecular, Instituto Mexicano del Seguro Social, Monterrey 64720, Mexico
Carlos Enrique Guerrero-Beltrán
Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey 64710, Mexico
Diana Resendez-Pérez
Departamento de Biología Celular y Genética, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza 66451, Mexico
Vianey González-Villasana
Departamento de Biología Celular y Genética, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza 66451, Mexico
Jesús Norberto Garza-González
Departmento de Ciencias Básicas, Vicerrectoría en Ciencias de la Salud, Universidad de Monterrey, San Pedro Garza García 66238, Mexico
Beatriz Silva-Ramírez
Centro de Investigación Biomédica del Noreste, Departamento de Inmunogenética, Instituto Mexicano del Seguro Social, Monterrey 64720, Mexico
Fabiola Castorena-Torres
Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey 64710, Mexico
Mario Bermúdez de León
Centro de Investigación Biomédica del Noreste, Departamento de Biología Molecular, Instituto Mexicano del Seguro Social, Monterrey 64720, Mexico
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 RT-qPCR 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.
