Mechanism of Action of Two Flavone Isomers Targeting Cancer Cells with Varying Cell Differentiation Status

Apoptosis can be triggered in two different ways, through the intrinsic or the extrinsic pathway. The intrinsic pathway is mediated by the mitochondria via the release of cytochrome C while the extrinsic pathway is prompted by death receptor signals and bypasses the mitochondria. These two pathways...

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Autores:
LeJeume, Timothy M.
Tsui, Hei Yin
Parsons, Laura B.
Miller, Gerald E.
Whitted, Crystal
Lynch, Kayla E.
Ramsauer, Robert E.
Tipo de recurso:
Article of journal
Fecha de publicación:
2015
Institución:
Universidad de Ciencias Aplicadas y Ambientales U.D.C.A
Repositorio:
Repositorio Institucional UDCA
Idioma:
eng
OAI Identifier:
oai:repository.udca.edu.co:11158/2571
Acceso en línea:
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142928
Palabra clave:
Apoptosis
Proteína Letal Asociada a bcl
Caspasa 10
Caspasa 8
Caspasa 9
Ciclo celular
Diferenciación celular
Línea Celular Tumoral
Proliferación Celular
Apoptosis
bcl-Associated Death Protein
Caspase 10
Caspase 8
Caspase 9
Cell Cycle
Cell Differentiation
Cell Line, Tumor
Cell Proliferation
Rights
openAccess
License
Derechos Reservados - Universidad de Ciencias Aplicadas y Ambientales
Description
Summary:Apoptosis can be triggered in two different ways, through the intrinsic or the extrinsic pathway. The intrinsic pathway is mediated by the mitochondria via the release of cytochrome C while the extrinsic pathway is prompted by death receptor signals and bypasses the mitochondria. These two pathways are closely related to cell proliferation and survival signaling cascades, which thereby constitute possible targets for cancer therapy. In previous studies we introduced two plant derived isomeric flavonoids, flavone A and flavone B which induce apoptosis in highly tumorigenic cancer cells of the breast, colon, pancreas, and the prostate. Flavone A displayed potent cytotoxic activity against more differentiated carcinomas of the colon (CaCo-2) and the pancreas (Panc28), whereas flavone B cytotoxic action is observed on poorly differentiated carcinomas of the colon (HCT 116) and pancreas (MIA PaCa). Apoptosis is induced by flavone A in better differentiated colon cancer CaCo-2 and pancreatic cancer Panc 28 cells via the intrinsic pathway by the inhibition of the activated forms of extracellular signal-regulated kinase (ERK) and pS6, and subsequent loss of phosphorylation of Bcl-2 associated death promoter (BAD) protein, while apoptosis is triggered by flavone B in poorly differentiated colon cancer HCT 116 and MIA PaCa pancreatic cancer cells through the extrinsic pathway with the concomitant upregulation of the phosphorylated forms of ERK and c-JUN at serine 73. These changes in protein levels ultimately lead to activation of apoptosis, without the involvement of AKT.