Identification of the anti-tumor activity and mechanisms of nuciferine through a network pharmacology approach

Abstract

Aim: Nuciferine is an aporphine alkaloid extracted from lotus leaves, which is a raw material in Chinese medicinal herb for weight loss. In this study we used a network pharmacology approach to identify the anti-tumor activity of nuciferine and the underlying mechanisms. Methods: The pharmacological activities and mechanisms of nuciferine were identified through target profile prediction, clustering analysis and functional enrichment analysis using our traditional Chinese medicine (TCM) network pharmacology platform. The antitumor activity of nuciferine was validated by in vitro and in vivo experiments. The anti-tumor mechanisms of nuciferine were predicted through network target analysis and verified by in vitro experiments. Results: The nuciferine target profile was enriched with signaling pathways and biological functions, including "regulation of lipase activity", "response to nicotine" and "regulation of cell proliferation". Target profile clustering results suggested that nuciferine to exert anti-tumor effect. In experimental validation, nuciferine (0.8 mg/mL) markedly inhibited the viability of human neuroblastoma SY5Y cells and mouse colorectal cancer CT26 cells in vitro, and nuciferine (0.05 mg/mL) significantly suppressed the invasion of 6 cancer cell lines in vitro. Intraperitoneal injection of nuciferine (9.5 mg/mL, ip, 3 times a week for 3 weeks) significantly decreased the weight of SY5Y and CT26 tumor xenografts in nude mice. Network target analysis and experimental validation in SY5Y and CT26 cells showed that the anti-tumor effect of nuciferine was mediated through inhibiting the PI3K-AKT signaling pathway and IL-1 levels in SY5Y and CT26 cells. Conclusion: By using a TCM network pharmacology method, nuciferine is identified as an anti-tumor agent against human neuroblastoma and mouse colorectal cancer in vitro and in vivo, through inhibiting the PI3K-AKT signaling pathways and IL-1 levels.

Lotus Leaf Extract Inhibits the Cell Migration and Metastasis of ER- Breast Cancer

“…However, few components of lotus leaf with the effects of anticancer have revealed so far. Previous studies showed that nuciferine, a major bioactive component of lotus, inhibits the growth of cancer cells and breast cancerassociated bone loss [25,53]. However, our results showed that nuciferine did not participate in LAE-inhibited migration.…”

“…All the collected filtrate was concentrated to dryness by evaporation on a rotary evaporator, and then dissolved in DMSO and filtered by a membrane filter with 0.22 µm pore size (Millipore, USA). Finally LAE was diluted into several concentrations (10,25,50, 100, 250 µg/ml) for cell treatments and stored at 4 o C.…”

“…Nuciferine, a major bioactive component of lotus, inhibits the growth of cancer cells and breast cancerassociated bone loss [24][25]. To verify if nuciferine is involved in the inhibition of cell migration, SK-BR-3, MDA-MB-231 and HCC1806 cells were treated with nuciferine supplement.…”

A Comprehensive Review on Chemical Profiling of Nelumbo Nucifera: Potential for Drug Development

“…The inhibitory mechanism of N. nucifera is associated with its ability to down-regulate connective tissue growth factor-induced PI3K/AKT/ ERK signaling (Chang et al, 2016). In line with this, inhibition of CT26 (colorectal cancer cells) tumor growth in nude mice by nuciferine is mediated through inhibiting the PI3K/AKT signaling pathway (Qi et al, 2016).…”

Traditional Chinese medicine for pulmonary fibrosis therapy: Progress and future prospects

“…Low drug productivity has been a significant problem for several decades even though numerous novel technologies were introduced during this period (Poornima et al, 2016). From a systems biology viewpoint, "network pharmacology", a hot spot that is utilized to construct the bioactive ingredient-target networks of herbs, is particularly suitable for the investigations of the bioactivity spectrum of TCM and the underlying mechanisms in PF (Ke et al, 2016;Qi et al, 2016;Wei et al, 2016). Therefore, to elucidate the pharmacological characteristics and mechanism of action of the formulas such as Hu-qi-yin, Shenlong Decoction, Decoction for Strengthening Qi and Replenishing Lung, and Sho-seiryu-to, more studies should be conducted on the effects and chemical profiles (including bioactive ingredients) to investigate the network of the role in the prevention and cure of PF before the follow-up trails in large amount of PF patients.…”