title: Synergistic antitumor effect of 5-fluorouracil in combination with parthenolide in human colorectal cancer.
abstract: Parthenolide (PT), a NF-κB 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 MTT, 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.
authors.affiliation: Department of Internal Medicine of Chonbuk National University Hospital, Chonbuk National University, Jeonju 561-712, Republic of Korea.
authors.forename: Se-Lim
authors.initials: SL
authors.lastname: Kim
authors.forename: Seong Hun
authors.initials: SH
authors.lastname: Kim
authors.forename: Kieu Thi Thu
authors.initials: KT
authors.lastname: Trang
authors.forename: In Hee
authors.initials: IH
authors.lastname: Kim
authors.forename: Seung-Ok
authors.initials: SO
authors.lastname: Lee
authors.forename: Soo Teik
authors.initials: ST
authors.lastname: Lee
authors.forename: Dae Ghon
authors.initials: DG
authors.lastname: Kim
authors.forename: Sang-Beom
authors.initials: SB
authors.lastname: Kang
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Kim
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D045304:Cytochromes c / Q000378:metabolism; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009368:Neoplasm Transplantation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D012717:Sesquiterpenes; C002669:parthenolide; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9; D005472:Fluorouracil