The Effect of Glucuronidation on Curcumin Bioactivity in Bone Metastatic Breast Cancer
Breast cancer bone metastasis is characterized by the formation of osteolytic lesions via a TGFβ-dependent vicious cycle. Although there is currently no cure for these lesions, previous studies show that turmeric-derived curcuminoids (CURC) may inhibit this pathway in estrogen receptor negative (...
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| Language: | en_US |
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The University of Arizona.
2017
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| Online Access: | http://hdl.handle.net/10150/624925 http://arizona.openrepository.com/arizona/handle/10150/624925 |
| Summary: | Breast cancer bone metastasis is characterized by the formation of osteolytic lesions via a
TGFβ-dependent vicious cycle. Although there is currently no cure for these lesions, previous
studies show that turmeric-derived curcuminoids (CURC) may inhibit this pathway in estrogen
receptor negative (ER–) breast cancers. However, most circulating CURC exists in its
glucuronidated form (G-CURC), so this study sought to determine the effects of glucuronidation
on CURC bioactivity in multiple ER– breast cancer cell lines. The results reveal that CURC
decreases phosphorylation of Smad proteins, a key step in the TGFβ signaling pathway, in
multiple ER– breast cancer cell lines, while G-CURC has no effect. Furthermore, secretion of
TGFβ-induced parathyroid hormone-related protein (PTHrP), a key osteolytic factor in bone
metastasis, was inhibited in ER– cells lines following CURC treatment and subsequent TGFβ
stimulation. These data suggest that aglycone CURC inhibits the Smad-dependent TGFβ
signaling pathway involved in the breast cancer bone metastases and may prevent release of
osteolytic factors that aid in bone resorption, while G-CURC is not biologically active. Since GCURC
is the predominate form in circulation, future studies are necessary to characterize the
means through which G-CURC may be converted to CURC, systematically and/or within the
bone microenvironment. |
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