Goyazensolide Induces Apoptosis in Cancer Cells in vitro and in vivo.

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 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 both in vivo and in 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.