Journal
CANCER LETTERS
Volume 335, Issue 2, Pages 479-486Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2013.03.007
Keywords
5-Fluorouracil; Parthenolide; Combination therapy; Anti-cancer; Colorectal cancer
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Funding
- Chonbuk National University Hospital Research Institute of Clinical Medicine
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Parthenolide (PT), a NF-kappa B inhibitor, has recently been demonstrated as a promising anticancer agent that promotes apoptosis of cancer cells. 5-fluorouracil (5-FU) has been a drug of choice for treatment of colorectal cancer (CRC). Unfortunately, many of the therapies that use 5-FU alone or in combination with other agents are likely to become ineffective due to drug resistance. In the present study, we investigated the antitumor effect of PT combined with 5-FU on a human CRC cell line, SW620. The results demonstrated that combination of PT and 5-FU induced apoptosis which was determined using MIT, cell cycle analysis, annexin-V assay, and Hoechst 33258 staining. Apoptosis through the mitochondrial pathway was confirmed by detecting regulation of Bcl-2 family members, cytochrome C release, and activation of caspase 3 and 9. Moreover, intra-peritoneal injection of PT and 5-FU showed significant inhibition of tumor growth in the xenograft model. These results demonstrate that PT exhibits anticancer activity in human colorectal cancer in vitro and in vivo. These findings provide an efficacious strategy to overcome 5-FU resistance in certain CRC. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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