TY  - JOUR
AU  - Echeverría, César
AU  - Martin, Aldo
AU  - Simon, Felipe
AU  - Salas, Cristian O.
AU  - Nazal, Mariajesus
AU  - Varela, Diego
AU  - Pérez-Castro, Ramón A.
AU  - Santibanez, Juan F.
AU  - Valdés-Valdés, Ricardo O.
AU  - Forero-Doria, Oscar
AU  - Echeverría, Javier
PY  - 2022
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1261
AB  - Background: There is abundant ethnopharmacological evidence the uses of regarding Solanum species as antitumor and anticancer agents. Glycoalkaloids are among the molecules with antiproliferative activity reported in these species.  Purpose: To evaluate the anticancer effect of the Solanum glycoalkaloid tomatine in hepatocellular carcinoma (HCC) in vitro (HepG2 cells) and in vivo models.  Methods: The resazurin reduction assay was performed to detect the effect of tomatine on cell viability in human HepG2 cell lines. Programmed cell death was investigated by means of cellular apoptosis assays using Annexin V. The expression of cancer related proteins was detected by Western blotting (WB). Reactive oxygen species (ROS) and calcium were determined by 2,7-dichlorodihydrofluorescein diacetate and Fluo-4, respectively. Intrahepatic HepG2 xenograft mouse model was used to elucidate the effect of tomatine on tumor growth in vivo.  Results and Discussion: Tomatine reduced HepG2 cell viability and induced the early apoptosis phase of cell death, consistently with caspase-3, -7, Bcl-2 family, and P53 proteins activation. Furthermore, tomatine increased intracellular ROS and cytosolic Ca+2 levels. Moreover, the NSG mouse xenograft model showed that treating mice with tomatine inhibited HepG2 tumor growth.  Conclusion: Tomatine inhibits in vitro and in vivo HCC tumorigenesis in part via modulation of p53, Ca+2, and ROS signalling. Thus, the results suggest the potential cancer therapeutic use of tomatine in HCC patients.
PB  - Frontiers Media S.A
T2  - Frontiers in Pharmacology
T1  - In Vivo and in vitro antitumor activity of tomatine in hepatocellular carcinoma
IS  - 9
SP  - 1003264
VL  - 13
DO  - 10.3389/fphar.2022.1003264
ER  - 

@article{
author = "Echeverría, César and Martin, Aldo and Simon, Felipe and Salas, Cristian O. and Nazal, Mariajesus and Varela, Diego and Pérez-Castro, Ramón A. and Santibanez, Juan F. and Valdés-Valdés, Ricardo O. and Forero-Doria, Oscar and Echeverría, Javier",
year = "2022",
abstract = "Background: There is abundant ethnopharmacological evidence the uses of regarding Solanum species as antitumor and anticancer agents. Glycoalkaloids are among the molecules with antiproliferative activity reported in these species.  Purpose: To evaluate the anticancer effect of the Solanum glycoalkaloid tomatine in hepatocellular carcinoma (HCC) in vitro (HepG2 cells) and in vivo models.  Methods: The resazurin reduction assay was performed to detect the effect of tomatine on cell viability in human HepG2 cell lines. Programmed cell death was investigated by means of cellular apoptosis assays using Annexin V. The expression of cancer related proteins was detected by Western blotting (WB). Reactive oxygen species (ROS) and calcium were determined by 2,7-dichlorodihydrofluorescein diacetate and Fluo-4, respectively. Intrahepatic HepG2 xenograft mouse model was used to elucidate the effect of tomatine on tumor growth in vivo.  Results and Discussion: Tomatine reduced HepG2 cell viability and induced the early apoptosis phase of cell death, consistently with caspase-3, -7, Bcl-2 family, and P53 proteins activation. Furthermore, tomatine increased intracellular ROS and cytosolic Ca+2 levels. Moreover, the NSG mouse xenograft model showed that treating mice with tomatine inhibited HepG2 tumor growth.  Conclusion: Tomatine inhibits in vitro and in vivo HCC tumorigenesis in part via modulation of p53, Ca+2, and ROS signalling. Thus, the results suggest the potential cancer therapeutic use of tomatine in HCC patients.",
publisher = "Frontiers Media S.A",
journal = "Frontiers in Pharmacology",
title = "In Vivo and in vitro antitumor activity of tomatine in hepatocellular carcinoma",
number = "9",
pages = "1003264",
volume = "13",
doi = "10.3389/fphar.2022.1003264"
}

Echeverría, C., Martin, A., Simon, F., Salas, C. O., Nazal, M., Varela, D., Pérez-Castro, R. A., Santibanez, J. F., Valdés-Valdés, R. O., Forero-Doria, O.,& Echeverría, J.. (2022). In Vivo and in vitro antitumor activity of tomatine in hepatocellular carcinoma. in Frontiers in Pharmacology
Frontiers Media S.A., 13(9), 1003264.
https://doi.org/10.3389/fphar.2022.1003264

Echeverría C, Martin A, Simon F, Salas CO, Nazal M, Varela D, Pérez-Castro RA, Santibanez JF, Valdés-Valdés RO, Forero-Doria O, Echeverría J. In Vivo and in vitro antitumor activity of tomatine in hepatocellular carcinoma. in Frontiers in Pharmacology. 2022;13(9):1003264.
doi:10.3389/fphar.2022.1003264 .

Echeverría, César, Martin, Aldo, Simon, Felipe, Salas, Cristian O., Nazal, Mariajesus, Varela, Diego, Pérez-Castro, Ramón A., Santibanez, Juan F., Valdés-Valdés, Ricardo O., Forero-Doria, Oscar, Echeverría, Javier, "In Vivo and in vitro antitumor activity of tomatine in hepatocellular carcinoma" in Frontiers in Pharmacology, 13, no. 9 (2022):1003264,
https://doi.org/10.3389/fphar.2022.1003264 . .