ABSTRACT
Since the discovery of autophagy in the mid-2000s, the interest in autophagy-related processes within the scientific community has been burgeoning. Countless authors have investigated its function in cellular homeostasis, but arguably of higher importance is its role during pathology. Although primarily a catabolic process, in cancer cells autophagy has numerous downstream effects, being observed to be both pro- and anti-apoptotic. One of the primary factors mediating this differential role of autophagy is the accumulation or sequestration of reactive oxygen species (ROS). Until recently, despite its increasing popularity in the Western world, the efficacy of herbal supplements has been largely anecdotal. Herein, we reviewed the ten most commonly studied herbs in cancer research and their impact on ROS regulation, on the activation and inhibition of autophagy, and ultimately on cancer cell death.
Subject(s)
Autophagy/drug effects , Herbal Medicine , Neoplasms/drug therapy , Neoplasms/metabolism , Reactive Oxygen Species/metabolism , Animals , Biomarkers , Gene Expression Regulation, Neoplastic/drug effects , Herbal Medicine/methods , Humans , Neoplasms/etiology , Neoplasms/pathology , Oxidation-Reduction/drug effects , Signal Transduction/drug effectsABSTRACT
NELL-1 is a secreted, osteoinductive protein whose expression rheostatically controls skeletal ossification. Overexpression of NELL-1 results in craniosynostosis in humans and mice, whereas lack of Nell-1 expression is associated with skeletal undermineralization. Here we show that Nell-1-haploinsufficient mice have normal skeletal development but undergo age-related osteoporosis, characterized by a reduction in osteoblast:osteoclast (OB:OC) ratio and increased bone fragility. Recombinant NELL-1 binds to integrin ß1 and consequently induces Wnt/ß-catenin signalling, associated with increased OB differentiation and inhibition of OC-directed bone resorption. Systemic delivery of NELL-1 to mice with gonadectomy-induced osteoporosis results in improved bone mineral density. When extended to a large animal model, local delivery of NELL-1 to osteoporotic sheep spine leads to significant increase in bone formation. Altogether, these findings suggest that NELL-1 deficiency plays a role in osteoporosis and demonstrate the potential utility of NELL-1 as a combination anabolic/antiosteoclastic therapeutic for bone loss.