Intestinal Research

Original Articles

Balsalazide Potentiates Parthenolide-Mediated Inhibition of Nuclear Factor-κB Signaling in HCT116 Human Colorectal Cancer Cells: Hyun-Young Kim, Se-Lim Kim, Young-Ran Park, Yu-Chuan Liu, Seung Young Seo, Seong Hun Kim, In Hee Kim, Seung Ok Lee, Soo Teik Lee, Sang Wook Kim; Intest Res 2015;13(3):233-241. Published online June 9, 2015; DOI: https://doi.org/10.5217/ir.2015.13.3.233

Background/Aims

Balsalazide is an anti-inflammatory drug used in the treatment of inflammatory bowel disease. Balsalazide can reduce inflammatory responses via several mechanisms, including inhibition of nuclear factor-κB (NF-κB) activity. Parthenolide (PT) inhibits NF-κB and exerts promising anticancer effects by promoting apoptosis. The present investigated the antitumor effects of balsalazide, combined with PT, on NF-κB in a representative human colorectal carcinoma cell line, HCT116.

Methods

We counted cells and conducted annexin-V assays and cell cycle analysis to measure apoptotic cell death. Western blotting was used investigate the levels of proteins involved in apoptosis.

Results

PT and balsalazide produced synergistic anti-proliferative effects and induced apoptotic cell death. The combination of balsalazide and PT markedly suppressed nuclear translocation of the NF-κB p65 subunit and the phosphorylation of inhibitor of NF-κB. Moreover, PT and balsalazide dramatically enhanced NF-κB p65 phosphorylation. Apoptosis, through the mitochondrial pathway, was confirmed by detecting effects on Bcl-2 family members, cytochrome c release, and activation of caspase-3 and -8.

Conclusions

Combination treatment with PT and balsalazide may offer an effective strategy for the induction of apoptosis in HCT116 cells.

Citations

Citations to this article as recorded by

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Frontiers in Genetics.2020;[Epub] CrossRef
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Parthenolide Sensitizes Human Colorectal Cancer Cells to Tumor Necrosis Factor-related Apoptosis-inducing Ligand through Mitochondrial and Caspase Dependent Pathway: Kieu Thi Thu Trang, Se-Lim Kim, Sang-Bae Park, Seung-Young Seo, Chung-Hwan Choi, Jin-Kyoung Park, Jin-Chang Moon, Soo-Teik Lee, Sang-Wook Kim; Intest Res 2014;12(1):34-41. Published online January 28, 2014; DOI: https://doi.org/10.5217/ir.2014.12.1.34

Abstract PDF PubReader

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.

Citations

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Nano magnetic liposomes-encapsulated parthenolide and glucose oxidase for ultra-efficient synergistic antitumor therapy
Wenbin Gao, Shipan Wei, Zhuo Li, Lei Li, Xuwu Zhang, Chunhui Li, Dawei Gao
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Anticancer and apoptotic activities of parthenolide in combination with epirubicin in mda-mb-468 breast cancer cells
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Journal of Cellular and Molecular Medicine.2018; 22(10): 4899. CrossRef
Combined Parthenolide and Balsalazide Have Enhanced Antitumor Efficacy Through Blockade of NF-κB Activation
Se-Lim Kim, Seong Hun Kim, Young Ran Park, Yu-Chuan Liu, Eun-Mi Kim, Hwan-Jeong Jeong, Yo Na Kim, Seung Young Seo, In Hee Kim, Seung Ok Lee, Soo Teik Lee, Sang-Wook Kim
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Chemico-Biological Interactions.2015; 228: 46. CrossRef
Balsalazide Potentiates Parthenolide-Mediated Inhibition of Nuclear Factor-κB Signaling in HCT116 Human Colorectal Cancer Cells
Hyun-Young Kim, Se-Lim Kim, Young-Ran Park, Yu-Chuan Liu, Seung Young Seo, Seong Hun Kim, In Hee Kim, Seung Ok Lee, Soo Teik Lee, Sang Wook Kim
Intestinal Research.2015; 13(3): 233. CrossRef
Goniothalamin enhances TRAIL-induced apoptosis in colorectal cancer cells through DR5 upregulation and cFLIP downregulation
THANET SOPHONNITHIPRASERT, SIRINUN NILWARANGKOON, YUKIO NAKAMURA, RAMIDA WATANAPOKASIN
International Journal of Oncology.2015; 47(6): 2188. CrossRef

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11 Crossref

Synergistic Effect of Parthenolide in Combination with 5-Fluorouracil in SW480 Cells: Se-Lim Kim, Thu Trang Thi Kieu , Byung Jun Jeon, Seong Hun Kim, In Hee Kim, Seung Ok Lee, Soo Teik Lee, Sang Wook Kim; Intest Res 2012;10(4):357-364. Published online October 31, 2012; DOI: https://doi.org/10.5217/ir.2012.10.4.357

Abstract PDF

Background/Aims
Parthenolide (PT) is responsible for the bioactivities of Feverfew. Besides its potent anti-inflammatory effect, this compound has recently been reported to induce apoptosis in cancer cells. Unfortunately, many of the therapies that use 5-fluorouracil (5-FU) alone or in combination with other agents are likely to become ineffective due to drug resistance. In the present study, we investigate the antitumor effect of PT combined with 5-FU on colorectal cancer cells. Methods: SW480 cell was employed as a representative of human colorectal carcinoma (CRC) cells. We performed MTT, annexin-V assay, and Hoechst 33258 staining to measure the synergistic effect. Western blotting was used to demonstrate apoptotic pathway. Results: Our result demonstrated that PT inhibited the viability of colorectal cancer cells and had synergistic anti-proliferation in combination with 5-FU. After combined treatment of 5-FU and PT, enhanced apoptotic cell death is observed using annexin-V FITC assay and it was revealed by the condensed chromatin and fragmented DNA. Compared with 5-FU or PT alone, the apoptosis of colorectal cancer cells treated with PT and 5-FU enhanced the activation of caspase-8, caspase-3. Conclusions: Combined treatment with PT may offer an efficacious strategy to overcome 5-FU resistance in certain CRC cells. (Intest Res 2012;10:357-364)

Citations

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Balsalazide Potentiates Parthenolide-Mediated Inhibition of Nuclear Factor-κB Signaling in HCT116 Human Colorectal Cancer Cells
Hyun-Young Kim, Se-Lim Kim, Young-Ran Park, Yu-Chuan Liu, Seung Young Seo, Seong Hun Kim, In Hee Kim, Seung Ok Lee, Soo Teik Lee, Sang Wook Kim
Intestinal Research.2015; 13(3): 233. CrossRef

3,023 View
32 Download
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