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

doi:10.3390/molecules26195742

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^*

^*Corresponding author for this work

Departamento Académico

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

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.

Original language	English
Article number	5742
Journal	Molecules
Volume	26
Issue number	19
DOIs	https://doi.org/10.3390/molecules26195742
Publication status	Published - 1 Oct 2021

Bibliographical note

Funding 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 Information:
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.

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

All Science Journal Classification (ASJC) codes

Analytical Chemistry
Chemistry (miscellaneous)
Molecular Medicine
Pharmaceutical Science
Drug Discovery
Physical and Theoretical Chemistry
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3390/molecules26195742

Cite this

Ramírez-flores, P. N., Barraza-reyna, P. J., Aguirre-vázquez, A., Camacho-moll, M. E., Guerrero-beltrán, C. E., Resendez-pérez, D., González-villasana, V., Garza-gonzález, J. N., Silva-ramírez, B., Castorena-torres, F., & de León, M. B. (2021). Isotretinoin and thalidomide down-regulate c-MYC gene expression and modify proteins associated with cancer in hepatic cells. Molecules, 26(19), Article 5742. https://doi.org/10.3390/molecules26195742

@article{2ba54c2a9af440a79d05b2417274418e,

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

abstract = "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.",

author = "Ram{\'i}rez-flores, {Patricia Nefertari} and Barraza-reyna, {Paulina J.} and Alain Aguirre-v{\'a}zquez and Camacho-moll, {Mar{\'i}a E.} and Guerrero-beltr{\'a}n, {Carlos Enrique} and Diana Resendez-p{\'e}rez and Vianey Gonz{\'a}lez-villasana and Garza-gonz{\'a}lez, {Jes{\'u}s Norberto} and Beatriz Silva-ram{\'i}rez and Fabiola Castorena-torres and {de Le{\'o}n}, {Mario Berm{\'u}dez}",

note = "Funding 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 P{\'a}ramo for his administrative support, and Biol. Jes{\'u}s Pablo G{\'o}mez 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 Information: 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. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = oct,

day = "1",

doi = "10.3390/molecules26195742",

language = "English",

volume = "26",

journal = "Molecules",

issn = "1420-3049",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "19",

}

Ramírez-flores, PN, Barraza-reyna, PJ, Aguirre-vázquez, A, Camacho-moll, ME, Guerrero-beltrán, CE, Resendez-pérez, D, González-villasana, V, Garza-gonzález, JN, Silva-ramírez, B, Castorena-torres, F & de León, MB 2021, 'Isotretinoin and thalidomide down-regulate c-MYC gene expression and modify proteins associated with cancer in hepatic cells', Molecules, vol. 26, no. 19, 5742. https://doi.org/10.3390/molecules26195742

TY - JOUR

T1 - Isotretinoin and thalidomide down-regulate c-MYC gene expression and modify proteins associated with cancer in hepatic cells

AU - Ramírez-flores, Patricia Nefertari

AU - Barraza-reyna, Paulina J.

AU - Aguirre-vázquez, Alain

AU - Camacho-moll, María E.

AU - Guerrero-beltrán, Carlos Enrique

AU - Resendez-pérez, Diana

AU - González-villasana, Vianey

AU - Garza-gonzález, Jesús Norberto

AU - Silva-ramírez, Beatriz

AU - Castorena-torres, Fabiola

AU - de León, Mario Bermúdez

N1 - Funding 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 Information: 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. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/10/1

Y1 - 2021/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85115697023&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85115697023&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/c4822f45-2bb1-329f-b197-4c5b479f592a/

U2 - 10.3390/molecules26195742

DO - 10.3390/molecules26195742

M3 - Article

C2 - 34641286

AN - SCOPUS:85115697023

SN - 1420-3049

VL - 26

JO - Molecules

JF - Molecules

IS - 19

M1 - 5742

ER -

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this