Neferine, an alkaloid ingredient in lotus seed embryo, inhibits proliferation of human osteosarcoma cells by promoting p38 MAPK-mediated p21 stabilization.
ABSTRACT Identification of natural products that have antitumor activity is invaluable to the chemoprevention and therapy of cancer. The embryos of lotus (Nelumbo nucifera) seeds are consumed in beverage in some parts of the world for their presumed health-benefiting effects. In this report we studied the effects of neferine, a major alkaloid component in lotus embryos, on human osteosarcoma cells and the underlying mechanisms. We found that neferine possessed a potent growth-inhibitory effect on human osteosarcoma cells, but not on non-neoplastic human osteoblast cells. The inhibitory effect of neferine on human osteosarcoma cells was largely attributed to cell cycle arrest at G1. The induction of G1 arrest was p21(WAF1/CIP1)-dependent, but was independent of p53 or RB (retinoblastoma-associated protein). The up-regulation of p21 by neferine was due to an increase in the half-life of p21 protein. We examined four kinases that are known to affect the stabilization of p21, and found that p38 MAPK and JNK were activated by neferine. However, only SB203580 (an inhibitor of p38), but not SP600125 (the inhibitor of JNK), can attenuate the up-regulation of p21 in response to neferine. Furthermore, the p21-stabilizing effect of neferine was abolished when p38 was silenced by RNA interference. Finally, we showed that neferine treatment led to an increased phosphorylation of p21 at Ser130 that was dependent on p38. Our results for the first time showed a direct antitumor effect of neferine, suggesting that consumption of neferine may have cancer-preventive and cancer-therapeutic benefit.
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ABSTRACT: Thai medicine has a long tradition of tonifying medicinal plants. In the present investigation, we studied the flower extracts of Jasminum sambac, Mammea siamensis, Mesua ferrea, Michelia alba, Mimusops elengi, and Nelumbo nucifera and speculated that these plants might influence metabolism and substance flow in the body.Journal of ethnopharmacology 06/2014; · 2.32 Impact Factor
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ABSTRACT: Diabetes mellitus has been identified as a major risk factor for cardiovascular diseases. High glucose-induced endothelial dysfunction and apoptosis is an important pathological feature of diabetic vasculopathy. Neferine, an alkaloid ingredient in lotus seed embryo has many biological actions such as anticancer and antioxidant. But little is known about whether Neferine protects endothelial cells against high glucose-induced oxidative stress and apoptosis. The present study was conducted to investigate the preventive effects of Neferine on hyperglycemia-induced injury of human umbilical vein endothelial cells (HUVECs). Our study showed that Neferine pretreatment effectively suppressed high glucose-induced HUVECs apoptosis. Also, Neferine pretreatment inhibited the augment of reactive oxygen species (ROS) in high glucose-treated HUVECs. The changes of SOD and MDA level in high glucose-treated HUVECs were also prevented by Neferine. Further study showed that Neferine did not affect the phosphorylation of JNK and p38 in high glucose-treated HUVECs. Interestingly, Neferine markedly inhibited high glucose-induced activation of PI3K/Akt pathway in HUVECs. High glucose-induced activation of NF-κB signal was also obviously suppressed by Neferine pretreatment. Collectively, we found that Neferine inhibited high glucose-induced endothelial apoptosis via blocking ROS/Akt/NF-κB pathway, which provides the evidence for using Neferine to treat diabetic vasculopathy.Endocrine 03/2014; · 3.53 Impact Factor
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ABSTRACT: Doxorubicin (DOX) is the best anticancer agent that has ever been used, but acquired tumor resistance and dose limiting toxicity are major road blocks. Concomitant use of natural compounds is a promising strategy to overcome this problem. Neferine, a proven anticancer-agent is found in green embryos of lotus seed. The study demonstrates that neferine acts as an effective enhancer of DOX-induced cell death in A549 cells through ROS mediated apoptosis with MAPK activation and inhibition of NF-κB nuclear translocation. Cotreatment of cells with neferine significantly enhanced intracellular DOX-accumulation. Neferine and DOX in combination also triggered oxidative stress through intracellular Ca2+ accumulation and dissipation of mitochondrial membrane potential in addition to significant loss of cellular antioxidant pool. The MAPK inhibitor effectively decreased the cell-death induced by neferine and DOX. Pretreatment of cells with glutathione reversed the apoptosis induced by the combined regimen and recovered the Bcl2/Bax ratio. Moreover, neferine treatment significantly increased the cell viability of DOX-treated cardiomyocytes indicating a possible protective role of neferine towards DOX-induced cardiotoxicity. Taken together, our results suggest that a strategy of using neferine and DOX in combination could be helpful to increase the efficacy of DOX and to achieve anticancer synergism by curbing the toxicity.Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 03/2014; · 2.99 Impact Factor