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Parthenolide Sensitizes Human Colorectal Cancer Cells to Tumor Necrosis Factor-related Apoptosis-inducing Ligand through Mitochondrial and Caspase Dependent Pathway
Intestinal Research ; : 34-41, 2014.
Artigo em Inglês | WPRIM | ID: wpr-113281
ABSTRACT
BACKGROUND/

AIMS:

Combination therapy utilizing tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in conjunction with other anticancer agents, is a promising strategy to overcome TRAIL resistance in malignant cells. Recently, parthenolide (PT) has proved to be a promising anticancer agent, and several studies have explored its use in combination therapy. Here, we investigated the molecular mechanisms by which PT sensitizes colorectal cancer (CRC) cells to TRAIL-induced apoptosis.

METHODS:

HT-29 cells (TRAIL-resistant) were treated with PT and/or TRAIL for 24 hours. The inhibitory effect on proliferation was detected using the 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Annexin V staining, cell cycle analysis, and Hoechst 33258 staining were used to assess apoptotic cell death. Activation of an apoptotic pathway was confirmed by Western blot.

RESULTS:

Treatment with TRAIL alone inhibited the proliferation of HCT 116 cells in a dose-dependent manner, whereas proliferation was not affected in HT-29 cells. Combination PT and TRAIL treatment significantly inhibited cell growth and induced apoptosis of HT-29 cells. We observed that the synergistic effect was associated with misregulation of B-cell lymphoma 2 (Bcl-2) family members, release of cytochrome C to the cytosol, activation of caspases, and increased levels of p53.

CONCLUSION:

Combination therapy using PT and TRAIL might offer an effetive strategy to overcome TRAIL resistance in certain CRC cells.
Assuntos

Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Neoplasias Colorretais / Ciclo Celular / Western Blotting / Linfoma de Células B / Fator de Necrose Tumoral alfa / Morte Celular / Apoptose / Anexina A5 / Células HT29 / Caspases Limite: Humanos Idioma: Inglês Revista: Intestinal Research Ano de publicação: 2014 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Neoplasias Colorretais / Ciclo Celular / Western Blotting / Linfoma de Células B / Fator de Necrose Tumoral alfa / Morte Celular / Apoptose / Anexina A5 / Células HT29 / Caspases Limite: Humanos Idioma: Inglês Revista: Intestinal Research Ano de publicação: 2014 Tipo de documento: Artigo