Intest Res.  2012 Oct;10(4):357-364. 10.5217/ir.2012.10.4.357.

Synergistic Effect of Parthenolide in Combination with 5-Fluorouracil in SW480 Cells

• Kim SL
• Kieu TT
• Jeon BJ
• Kim SH
• Kim IH
• Lee SO
• Lee ST
• Kim SW

• KMID: 2174252
• DOI: http://doi.org/10.5217/ir.2012.10.4.357

Abstract

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.

Keyword

Parthenolide; 5-Fluorouracil; Apoptosis; Colorectal Neoplasms

MeSH Terms

Apoptosis
Bisbenzimidazole
Blotting, Western
Caspase 8
Cell Death
Chromatin
Colorectal Neoplasms
DNA
Drug Resistance
Fluorescein-5-isothiocyanate
Fluorouracil
Humans
Sesquiterpenes
Tanacetum parthenium
Bisbenzimidazole
Caspase 8
Chromatin
DNA
Fluorescein-5-isothiocyanate
Fluorouracil
Sesquiterpenes