title: Goyazensolide Induces Apoptosis in Cancer Cellsin vitroandin vivo.
abstract: As part of the screening program for anticancer agents from natural sources, the sesquiterpene lactone goyazensolide (GZL) was identified as a potent NF-κB inhibitor. The hollow-fiber assay was used to evaluate the anti-tumor efficacy of GZLin vivo. The mechanistic effects of GZL were evaluated in the HT-29 colonic cell line to reveal the pathway through which GZL exerts its effects. NF-κB subunits p65 and p50 were inhibited, and the upstream mediator IκB kinase (IKKβ) was downregulated in a dose-dependent manner. Apoptosis was mediated by caspase-3, and cell cycle arrest was detected in G1-phase. Consequently, 96% of the cell population was in sub G1-phase after treatment with GZL (10 μM).The antitumor effect of GZL was observed at a dose of 12.5 mg/kg. Cell adhesion was affected as a result of NF-κB inhibition. GZL appears to selectively target the transcription factor NF-κB. In summary, GZL sensitizes HT-29 colon cancer cells to apoptosis and cell death in a dose-dependent manner bothin vivoandin vitro, through NF-κB inhibition (IC50= 3.8 μM). Thus, it is a new potent lead compound for further development into a new effective chemotherapeutic agent.
authors.affiliation: Division of Pharmacy Practice and Administration, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210 ; Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210.
authors.forename: Ulyana Muñoz
authors.initials: UM
authors.lastname: Acuña
authors.affiliation: Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612.
authors.forename: Qi
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Lantvit
authors.affiliation: Division of Pharmacy Practice and Administration, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210 ; Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Wittwer
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210.
authors.forename: A Douglas
authors.initials: AD
authors.lastname: Kinghorn
authors.affiliation: Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Swanson
authors.affiliation: Division of Pharmacy Practice and Administration, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210 ; Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210.
authors.forename: Esperanza J Carcache
authors.initials: EJ
authors.lastname: de Blanco
keywords: Goyazensolide; NF-κB; ROS; adhesion; apoptosis; caspase-3