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KMID : 0988920140120010034
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Intestinal Research
2014 Volume.12 No. 1 p.34 ~ p.41
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Parthenolide Sensitizes Human Colorectal Cancer Cells to Tumor Necrosis Factor-related Apoptosis-inducing Ligand through Mitochondrial and Caspase Dependent Pathway
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Trang Kieu Thi Thu
Kim Se-Lim
Park Sang-Bae
Seo Seung-Young
Choi Chung-Hwan
Park Jin-Kyoung
Moon Jin-Chang
Lee Soo-Teik
Kim Sang-Wook
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Abstract
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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 treatmentsignificantly inhibited cell growth and induced apoptosis of HT-29 cells. We observed that the synergistic effect was associatedwith 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. (Intest Res 2014;12:34-41)
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KEYWORD
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Parthenolide, TRAIL, Colorectal neoplasm, TRAIL resistance, Apoptosis
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