Pro- and anti-tumor effects of wedelolactone in breast cancer cells
| Autoři | |
|---|---|
| Rok publikování | 2013 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Natural phytocompounds and their derivatives are commonly used for prevention and treatment of various diseases, including cancer. Wedelolactone is one of the active polyphenolic compounds in extracts of Wedelia calandulaceae and Eclipta prostrata. Wedelolactone was shown to inhibit growth of breast and prostate cancer cells in vitro and in vivo. The growth inhibitory effects of wedelolactone have been largely attributed to the inhibition of IKK kinase, the key enzyme regulating the activity of NFkB. We have recently described that wedelolactone inhibits DNA synthesis and acts as catalytic inhibitor of DNA topoisomerase IIalpha. This study was designed to characterize the mechanisms of wedelolactone effects on breast cancer cells in detail. We observed that in nM concentrations, wedelolactone stimulates growth of ER-positive breast cancer cells MCF-7 and T47D by activation of genomic ER-signalling pathway. This growth-stimulatory effect was not detected in ER-negative MDA-MB-231 breast cancer cells. In uM concentrations, wedelolactone inhibits ERK but activates p53, JNK-signalling pathway and induces apoptosis of both ER-positive and ER-negative breast cancer cells. Pro-apoptotic effects of wedelolactone are enhanced by ERK inhibition but reduced by JNK and ER inhibitors. Lastly, wedelolactone-induced cytotoxicity to breast cancer cells was enhanced in hypoxic and acidic tissue culture conditions. We conclude that depending on concentration, wedelolactone can act both as tumor promoter and tumor suppressor in ER-positive breast cancer cells while only tumor suppression was detected in ER-negative cells. Interestingly, pro-apoptotic effects of wedelolactone on breast cancer cells are enhanced in specific features of tumor microenvironment. |
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