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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Drug+Des+Devel+Ther
2015 ; 9
(ä): 5511-51
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
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English Wikipedia
Plumbagin suppresses epithelial to mesenchymal transition and stemness via
inhibiting Nrf2-mediated signaling pathway in human tongue squamous cell
carcinoma cells
#MMPMID26491260
Pan ST
; Qin Y
; Zhou ZW
; He ZX
; Zhang X
; Yang T
; Yang YX
; Wang D
; Zhou SF
; Qiu JX
Drug Des Devel Ther
2015[]; 9
(ä): 5511-51
PMID26491260
show ga
Tongue squamous cell carcinoma (TSCC) is the most common malignancy in oral and
maxillofacial tumors with highly metastatic characteristics. Plumbagin
(5-hydroxy-2-methyl-1, 4-naphthoquinone; PLB), a natural naphthoquinone derived
from the roots of Plumbaginaceae plants, exhibits various bioactivities,
including anticancer effects. However, the potential molecular targets and
underlying mechanisms of PLB in the treatment of TSCC remain elusive. This study
employed stable isotope labeling by amino acids in cell culture (SILAC)-based
quantitative proteomic approach to investigate the molecular interactome of PLB
in human TSCC cell line SCC25 and elucidate the molecular mechanisms. The
proteomic data indicated that PLB inhibited cell proliferation, activated death
receptor-mediated apoptotic pathway, remodeled epithelial adherens junctions
pathway, and manipulated nuclear factor erythroid 2-related factor 2
(Nrf2)-mediated oxidative stress response signaling pathway in SCC25 cells with
the involvement of a number of key functional proteins. Furthermore, we verified
these protein targets using Western blotting assay. The verification results
showed that PLB markedly induced cell cycle arrest at G2/M phase and extrinsic
apoptosis, and inhibited epithelial to mesenchymal transition (EMT) and stemness
in SCC25 cells. Of note, N-acetyl-l-cysteine (NAC) and l-glutathione (GSH)
abolished the effects of PLB on cell cycle arrest, apoptosis induction, EMT
inhibition, and stemness attenuation in SCC25 cells. Importantly, PLB suppressed
the translocation of Nrf2 from cytosol to nucleus, resulting in an inhibition in
the expression of downstream targets. Taken together, these results suggest that
PLB may act as a promising anticancer compound via inhibiting Nrf2-mediated
oxidative stress signaling pathway in SCC25 cells. This study provides a clue to
fully identify the molecular targets and decipher the underlying mechanisms of
PLB in the treatment of TSCC.