Journal
PROTEOMICS CLINICAL APPLICATIONS
Volume 1, Issue 4, Pages 410-419Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/prca.200600798
Keywords
aloe-emodin; anticancer
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Aloe-emodin (AE) is one of the main bioactive anthraquinones of Rheum palmatum, a widely used herbal medicine. Several recent studies suggested that AE possesses potent anticancer properties, although the mechanisms are yet to be fully elucidated. The present study aimed to identify the molecular targets of AE in a human hepatocellular carcinoma cell line, HepG2. We first found that AE was more cytotoxic and effective in inducing apoptosis and cell cycle arrest than its analog emodin (EM). Proteomic study using 2-D DIGE revealed that AE affected multiple proteins associated with oxidative stress, cell cycle arrest, antimetastasis, and hepatitis C virus replication. For example, peroxiredoxins (PRDX) and DJ-1, both of which are redox-sensitive proteins, were among those markedly up-regulated, suggesting the presence of oxidative stress in AE-treated cells. Further biochemical studies demonstrated that AE enhanced the intracellular level of reactive oxygen species and oxidation of PRDX-2, -4, and DJ-1. in addition, AE inhibited DNA synthesis via up-regulation of the CDK4 inhibitor p16 and inhibition of Rb phosphorylation. Furthermore, AE was able to decrease cell migration via up-regulation of the metastasis inhibitor, nm23. Taken together, AE induced anticancer effects in HepG2 cells via multiple pathways by affecting different protein targets.
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