AIM: As part of an on going investigation of novel anticancer agents from natural origin, the biological and cellular effects of (5Z)-7-oxozeaenol on cancer cells were investigated. MATERIALS AND METHODS: The expression of nuclear factor kappa B (NF-κB), IκB kinase (IKKα), IKKβ and caspase-3 were analyzed by western blot. Reactive oxygen species (ROS) fluorescence and caspase luminescent assays were used to assess the intracellular effects in HeLa cervical and HT-29 colon cancer cell lines. The mitochondrial transmembrane potential (MTP) was analyzed by fluorescence-activated cell sorting (FACS). RESULTS: Cells treated with (5Z)-7-oxozeaenol exhibited down-regulation of NF-κB in a dose-dependent manner. Treatment with (5Z)-7-oxozeaenol significantly enhanced the levels of ROS in HeLa and HT-29 cells. MTP was reduced in HT-29 cells. The expression of caspase-3 and -7 was induced in (5Z)-7-oxozeaenol treated HeLa cells, in comparison with those treated with paclitaxel. CONCLUSION: Our findings suggest that (5Z)-7-oxozeaenol is a potent inhibitor of the NF-κB pathway and potentiates the production of ROS, as well as induces caspase-3 and -7 in HeLa and HT-29 cancer cells. Thus, (5Z)-7-oxozeaenol represents a new lead compound for drug development, particularly as a new cancer chemotherapeutic agent, since programmed cell death might be mediated through the activation of a caspase-arbitrated pathway.
AIM: As part of an on going investigation of novel anticancer agents from natural origin, the biological and cellular effects of (5Z)-7-oxozeaenol on cancer cells were investigated. MATERIALS AND METHODS: The expression of nuclear factor kappa B (NF-κB), IκB kinase (IKKα), IKKβ and caspase-3 were analyzed by western blot. Reactive oxygen species (ROS) fluorescence and caspase luminescent assays were used to assess the intracellular effects in HeLa cervical and HT-29 colon cancer cell lines. The mitochondrial transmembrane potential (MTP) was analyzed by fluorescence-activated cell sorting (FACS). RESULTS: Cells treated with (5Z)-7-oxozeaenol exhibited down-regulation of NF-κB in a dose-dependent manner. Treatment with (5Z)-7-oxozeaenol significantly enhanced the levels of ROS in HeLa and HT-29 cells. MTP was reduced in HT-29 cells. The expression of caspase-3 and -7 was induced in (5Z)-7-oxozeaenol treated HeLa cells, in comparison with those treated with paclitaxel. CONCLUSION: Our findings suggest that (5Z)-7-oxozeaenol is a potent inhibitor of the NF-κB pathway and potentiates the production of ROS, as well as induces caspase-3 and -7 in HeLa and HT-29 cancer cells. Thus, (5Z)-7-oxozeaenol represents a new lead compound for drug development, particularly as a new cancer chemotherapeutic agent, since programmed cell death might be mediated through the activation of a caspase-arbitrated pathway.
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Authors: Ulyana Muñoz Acuña; Qi Shen; Yulin Ren; Daniel D Lantvit; Jennifer A Wittwer; A Douglas Kinghorn; Steven M Swanson; Esperanza J Carcache de Blanco Journal: Int J Cancer Res Date: 2013
Authors: Ulyana Muñoz Acuña; Susan Matthew; Li Pan; A Douglas Kinghorn; Steven M Swanson; Esperanza J Carcache de Blanco Journal: Phytother Res Date: 2013-12-12 Impact factor: 5.878
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