Abstract
BackgroundRoot bark of mulberry (Morus alba L.) has been used in herbal medicine as anti-phlogistic, liver protective, kidney protective, hypotensive, diuretic, anti-cough and analgesic agent. However, the anti-cancer activity and the potential anti-cancer mechanisms of mulberry root bark have not been elucidated. We performed in vitro study to investigate whether mulberry root bark extract (MRBE) shows anti-inflammatory and anti-cancer activity.MethodsIn anti-inflammatory activity, NO was measured using the griess method. iNOS and proteins regulating NF-κB and ERK1/2 signaling were analyzed by Western blot. In anti-cancer activity, cell growth was measured by MTT assay. Cleaved PARP, ATF3 and cyclin D1 were analyzed by Western blot.ResultsIn anti-inflammatory effect, MRBE blocked NO production via suppressing iNOS over-expression in LPS-stimulated RAW264.7 cells. In addition, MRBE inhibited NF-κB activation through p65 nuclear translocation via blocking IκB-α degradation and ERK1/2 activation via its hyper-phosphorylation. In anti-cancer activity, MRBE deos-dependently induced cell growth arrest and apoptosis in human colorectal cancer cells, SW480. MRBE treatment to SW480 cells activated ATF3 expression and down-regulated cyclin D1 level. We also observed that MRBE-induced ATF3 expression was dependent on ROS and GSK3β. Moreover, MRBE-induced cyclin D1 down-regulation was mediated from cyclin D1 proteasomal degradation, which was dependent on ROS.ConclusionsThese findings suggest that mulberry root bark exerts anti-inflammatory and anti-cancer activity.
Highlights
We evaluated whether mulberry root bark extract (MRBE) regulates cyclin D1 level in SW480 cells since cyclin D1 is associated with cell growth arrest and apoptosis
GSK3β and Reactive oxygen species (ROS)-dependent Activating transcription factor 3 (ATF3) activation of MRBE in SW480 cells To elucidate the molecular mechanism for MRBE-induced ATF3 expression, we evaluated several signaling pathways affected by MRBE
We found that MRBE-activated ATF3 expression was reduced by the treatments SB216763 (GSK3β inhibitor) and N-Acetyl Cysteine (NAC) (ROS scavenger), which indicates that MRBEinduced ATF3 expression could be dependent on GSK3β and ROS
Summary
The anti-cancer activity and the potential anti-cancer mechanisms of mulberry root bark have not been elucidated. We performed in vitro study to investigate whether mulberry root bark extract (MRBE) shows anti-inflammatory and anti-cancer activity. Inflammation is an innate immune response by various immune cells including macrophages for the protection against the harmful stimuli such as virus and bacteria [1]. As a consequence of excessive inflammatory response, large amounts inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2) are produced [2]. Inflammatory mediators-induced chronic inflammation is considered to be a cause of numerous human diseases including cancer, atherosclerosis, arthritis and septic shock [3,4,5]. NO is produced by inducible nitric oxide synthase (iNOS) and results in. Cancer chemoprevention has received a great attention and medicinal plants have been regarded as effective anti-cancer sources [13]
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