Open AccessGoyazensolide Induces Apoptosis in Cancer Cells in vitro and in vivo
Author(s) -
Ulyana Muñoz Acuña,
Qi Shen,
Yulin Ren,
Daniel D. Lantvit,
Jennifer Wittwer,
A. Douglas Kinghorn,
Steven M. Swanson,
Esperanza J. Carcache de Blanco
Publication year - 2013
Publication title -
international journal of cancer research
Language(s) - English
Resource type - Journals
eISSN - 1811-9735
pISSN - 1811-9727
DOI - 10.3923/ijcr.2013.36.53
Subject(s) - apoptosis , in vivo , iκb kinase , cell cycle checkpoint , cancer cell , in vitro , programmed cell death , cell cycle , nf κb , cell culture , cell , pharmacology , biology , chemistry , cancer , biochemistry , genetics , microbiology and biotechnology
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 GZL in 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 G 1 -phase. Consequently, 96% of the cell population was in sub G 1 -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 both in vivo and in vitro , through NF-κB inhibition (IC 50 = 3.8 μM). Thus, it is a new potent lead compound for further development into a new effective chemotherapeutic agent.