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Int J Mol Sci. 2016 Feb 22;17(2):260. doi: 10.3390/ijms17020260.

Chalcone-Induced Apoptosis through Caspase-Dependent Intrinsic Pathways in Human Hepatocellular Carcinoma Cells.

Author information

1
Laboratorio de Bionanotecnologia, Universidad Bernardo O Higgins, General Gana 1780, Santiago 8370854, Chile. rramirez@ubo.cl.
2
Departamento de Ciencias Químicas, Laboratorio de Síntesis Orgánica, Universidad Andres Bello, Av. República 275, Santiago 8370146, Chile. cescobar@unab.cl.
3
Laboratorio de Bionanotecnologia, Universidad Bernardo O Higgins, General Gana 1780, Santiago 8370854, Chile. valentina.romero@ubo.cl.
4
Laboratorio de Bionanotecnologia, Universidad Bernardo O Higgins, General Gana 1780, Santiago 8370854, Chile. montorfano3320@gmail.com.
5
Centro de Investigación y Tratamiento del Cancer, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile. ricardoarmisen@med.uchile.cl.
6
Center for Excellence in Precision Medicine Pfizer, Pfizer Chile, Obispo Arturo Espinoza Campos 2526, Macul, Santiago 7810305, Chile. ricardoarmisen@med.uchile.cl.
7
Urology Department, Hospital Barros Luco Trudeau, San Miguel, Santiago 8900085, Chile. vborgna@gmail.com.
8
Andes Biotechnologies SA and Fundación Ciencia para la Vida, Zañartu 1482, Ñuñoa, Santiago 7780272, Chile. vborgna@gmail.com.
9
Andes Biotechnologies SA and Fundación Ciencia para la Vida, Zañartu 1482, Ñuñoa, Santiago 7780272, Chile. e.jeldes1@gmail.com.
10
Department of Biological Science, Faculty of Biological Science, Universidad Andrés Bello, Santiago 8370146, Chile. e.jeldes1@gmail.com.
11
Instituto Nacional del Cancer, Universidad de Chile, Profesor Zañartu 1010, Santiago 8380455, Chile. drluispizarro@gmail.com.
12
Laboratorio de Fisiopatología Integrativa, Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas and Facultad de Medicina, Universidad Andres Bello, Avenida Republica 239, Santiago 8370146, Chile. fsimon@unab.cl.
13
Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile. fsimon@unab.cl.
14
Laboratorio de Bionanotecnologia, Universidad Bernardo O Higgins, General Gana 1780, Santiago 8370854, Chile. cesar.echeverria@ubo.cl.
15
Centro de Investigación y Tratamiento del Cancer, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile. cesar.echeverria@ubo.cl.

Abstract

Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide. Chemoprevention of HCC can be achieved through the use of natural or synthetic compounds that reverse, suppress or prevent the development of cancer progression. In this study, we investigated the antiproliferative effects and the mechanism of action of two compounds, 2,3,4'-trimethoxy-2'-hydroxy-chalcone (CH1) and 3'-bromo-3,4-dimethoxy-chalcone (CH2), over human hepatoma cells (HepG2 and Huh-7) and cultured mouse hepatocytes (HepM). Cytotoxic effects were observed over the HepG2 and Huh-7, and no effects were observed over the HepM. For HepG2 cells, treated separately with each chalcone, typical apoptotic laddering and nuclear condensation were observed. Additionally, the caspases and Bcl-2 family proteins activation by using Western blotting and immunocytochemistry were studied. Caspase-8 was not activated, but caspase-3 and -9 were both activated by chalcones in HepG2 cells. Chalcones also induced reactive oxygen species (ROS) accumulation after 4, 8 and 24 h of treatment in HepG2 cells. These results suggest that apoptosis in HepG2 was induced through: (i) a caspase-dependent intrinsic pathway; and (ii) by alterations in the cellular levels of Bcl-2 family proteins, and also, that the chalcone moiety could be a potent candidate as novel anticancer agents acting on human hepatomas.

KEYWORDS:

Caspase; Chalcone; Reactive Oxygen Species

PMID:
26907262
PMCID:
PMC4783989
DOI:
10.3390/ijms17020260
[Indexed for MEDLINE]
Free PMC Article

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