Selective antagonization of activated Nrf2 and inhibition of cancer cell proliferation by procyanidins from Cinnamomi Cortex extract

Selective antagonization of activated Nrf2 and inhibition of cancer cell proliferation by... Nuclear factor-E2-related factor 2 (Nrf2) is an important transcription factor and plays a central role in inducible expression of many cytoprotective genes. Recent studies have reported that various cancer cells having unrestrained Nrf2 due to its overexpression exhibit increased proliferation and resistance to chemotherapy. Suppression of abnormal Nrf2 activation is needed for a new therapeutic approach against these cancers. Our previous study found that procyanidins prepared from Cinnamomi Cortex extract (CCE) have an ability to suppress Nrf2-regulated enzyme activity and Nrf2 expression in human lung cancer A549 cells. In the present study, we investigated the effect of CCE procyanidins on Nrf2 activity and cell proliferation in several cancer cells, which have normal or constitutively active Nrf2. Interestingly, CCE procyanidin treatment selectively reduced Nrf2 expression and inhibited cell proliferation in cancer cells that overexpress Nrf2, but these phenomena were not seen in cells with low Nrf2 expression. Moreover, transfection assay demonstrated that CCE procyanidins had selective inhibition of activated Nrf2. These results suggest that CCE procyanidins might be an effective cancer therapeutic agent to selectively suppress abnormal Nrf2 activation responsible for enhanced proliferation. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Biochemistry and Biophysics Elsevier

Selective antagonization of activated Nrf2 and inhibition of cancer cell proliferation by procyanidins from Cinnamomi Cortex extract

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Publisher
Elsevier
Copyright
Copyright © 2015 Elsevier Inc.
ISSN
0003-9861
eISSN
1096-0384
D.O.I.
10.1016/j.abb.2015.09.007
Publisher site
See Article on Publisher Site

Abstract

Nuclear factor-E2-related factor 2 (Nrf2) is an important transcription factor and plays a central role in inducible expression of many cytoprotective genes. Recent studies have reported that various cancer cells having unrestrained Nrf2 due to its overexpression exhibit increased proliferation and resistance to chemotherapy. Suppression of abnormal Nrf2 activation is needed for a new therapeutic approach against these cancers. Our previous study found that procyanidins prepared from Cinnamomi Cortex extract (CCE) have an ability to suppress Nrf2-regulated enzyme activity and Nrf2 expression in human lung cancer A549 cells. In the present study, we investigated the effect of CCE procyanidins on Nrf2 activity and cell proliferation in several cancer cells, which have normal or constitutively active Nrf2. Interestingly, CCE procyanidin treatment selectively reduced Nrf2 expression and inhibited cell proliferation in cancer cells that overexpress Nrf2, but these phenomena were not seen in cells with low Nrf2 expression. Moreover, transfection assay demonstrated that CCE procyanidins had selective inhibition of activated Nrf2. These results suggest that CCE procyanidins might be an effective cancer therapeutic agent to selectively suppress abnormal Nrf2 activation responsible for enhanced proliferation.

Journal

Archives of Biochemistry and BiophysicsElsevier

Published: Nov 1, 2015

References

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