Downregulation of PI3K/Akt/mTOR signaling pathway in curcumin-induced autophagy in APP/PS1 double transgenic mice

Wang, Chen; Zhang, Xiong; Teng, Zhipeng; Zhang, Tong; Yu, Li

doi:10.1016/j.ejphar.2014.06.051

Cited by 180 publications

(106 citation statements)

References 30 publications

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“…These results demonstrate that curcumin performs its growth-inhibitory effect in LCSCs through the PI3K/AKT/mTOR signaling pathway. Curcumin can also impact the cell cycle progression, autophagy, invasion, epithelial-mesenchymal transition and angiogenesis of cancer cells through the PI3K/AKT signaling pathway, thus inhibiting the growth and metastasis of cancer (45)(46)(47)(48)(49). In addition, curcumin exerts an anti-inflammatory effect and protects cardiomyocytes against high glucose-induced apoptosis through this pathway (9,52).…”

Section: Discussionmentioning

confidence: 99%

Curcumin inhibits the growth of liver cancer stem cells through the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway

Wang

2018

Exp Ther Med

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Abstract. Cancer stem cells are considered as a main cause of cancer recurrence. In the present study, the effects of curcumin on the growth of liver cancer stem cells (LCSCs) were investigated. The proliferation and apoptosis of LCSCs were assessed by MTT assays and flow cytometry. Changes in the expression of apoptosis-related proteins were identified by western blotting.The results of the study demonstrated that curcumin treatment inhibited the growth of LCSCs, induced cell apoptosis, as well as regulated the expression of apoptosis-associated proteins and the release of cytochrome c. Further experiments revealed that treatment with curcumin inhibited that the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Treatment with an activator of PI3K/AKT reversed the curcumin-induced growth inhibition of LCSCs. These results demonstrated that curcumin inhibited the growth of LCSCs through the PI3K/AKT/mTOR signaling pathway. Thus, the present study suggested that curcumin may be a potentially efficient agent in the treatment of liver cancer. IntroductionLiver cancer is one of the most common malignancies worldwide, with ~600,000 new cases diagnosed annually (1). However, the 5-year survival rate of liver cancer is <9% (2). This tumor is the fourth cause of cancer-associated mortality, ranking second in men and sixth in women, with >250,000 mortalities annually (1,3-5). At present, surgical resection is the major therapeutic strategy for liver cancer, although a high rate of recurrence remains (6,7).Stem cells are a type of cells harboring the ability to self-renew and differentiate (8). Cancer stem cells are a subset of cancer cells with stem cell properties. Although radiotherapy and chemotherapy can eliminate the majority of tumor cells, cancer stem cells have the ability to self-renew and differentiate to generate tumor cell heterogeneity, and thus resist these therapies (9). Liver cancer stem cells (LCSCs) are considered to account for the chemotherapy resistance and recurrence of liver cancer (10,11). Multiple signals pathways, including Notch and Wnt/β-catenin, are found to serve important roles in the stemness of LCSCs (12). The regulation of LCSCs via the manipulation of internal signaling pathways may become a feasible treatment for patients with liver cancer.Curcumin is a yellow natural compound derived from Rhizoma curcumae longae and is widely used as a spice in Asia. Curcumin has been demonstrated to exert anti-inflammatory, antioxidant and antiangiogenic effects (13-15), while it also exerts a potential antitumor effect (15-17). However, the effects of curcumin on LCSCs remain unclear. Therefore, the aim of the present study was to examine the effects of curcumin on the growth of LCSCs, as well as the underlying mechanism of its action. The study demonstrated that treatment with curcumin is able to inhibit the growth of LCSCs, and this compound may be a promising treatment agent for liver cancer. Materials and methodsC...

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Section: Discussionmentioning

confidence: 99%

Curcumin inhibits the growth of liver cancer stem cells through the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway

Wang

2018

Exp Ther Med

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“…The PI3K/AKT/mTOR signalling pathway, which regulates autophagy, is downregulated. 23 The other study about the PI3K/AKT/GSK-3β signalling pathway showed that it can improve glucose homeostasis when upregulated. 24 Our results also showed that curcumin can upregulate the PI3K/AKT signalling pathway to reduce insulin resistance and improve cerebral glucose metabolism.…”

Section: Discussionmentioning

confidence: 99%

Curcumin ameliorates insulin signalling pathway in brain of Alzheimer’s disease transgenic mice

Feng

Dang

Fan

et al. 2016

Int J Immunopathol Pharmacol

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Deficits in glucose, impaired insulin signalling and brain insulin resistance are common in the pathogenesis of Alzheimer's disease (AD); therefore, some scholars even called AD type 3 diabetes mellitus. Curcumin can reduce the amyloid pathology in AD. Moreover, it is a well-known fact that curcumin has anti-oxidant and anti-inflammatory properties. However, whether or not curcumin could regulate the insulin signal transduction pathway in AD remains unclear. In this study, we used APPswe/PS1dE9 double transgenic mice as the AD model to investigate the mechanisms and the effects of curcumin on AD. Immunohistochemical (IHC) staining and a western blot analysis were used to test the major proteins in the insulin signal transduction pathway. After the administration of curcumin for 6 months, the results showed that the expression of an insulin receptor (InR) and insulin receptor substrate (IRS)-1 decreased in the hippocampal CA1 area of the APPswe/PS1dE9 double transgenic mice, while the expression of phosphatidylinositol-3 kinase (PI3K), phosphorylated PI3K (p-PI3K), serine-threonine kinase (AKT) and phosphorylated AKT (p-AKT) increased. Among the curcumin groups, the medium-dose group was the most effective one. Thus, we believe that curcumin may be a potential therapeutic agent that can regulate the critical molecules in brain insulin signalling pathways. Furthermore, curcumin could be adopted as one of the AD treatments to improve a patient's learning and memory ability.

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“…This effect occurs through a new protective mechanism involving forkhead box protein O1 and may arise as a therapeutic target for the treatment of oxidative stress-related cardiovascular diseases . Finally, curcumin induces of autophagy by downregulating phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway in neurons from Alzheimer's disease animal models, which results in inhibition of Aβ generation and a neuroprotective effect (Wang et al, 2014).…”

Section: Curcuminmentioning

confidence: 99%

Inhibitors of dihydroceramide desaturase 1: Therapeutic agents and pharmacological tools to decipher the role of dihydroceramides in cell biology

Casasampere

Ordóñez

Pou

et al. 2016

Chemistry and Physics of Lipids

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Downregulation of PI3K/Akt/mTOR signaling pathway in curcumin-induced autophagy in APP/PS1 double transgenic mice

Cited by 180 publications

References 30 publications

Curcumin inhibits the growth of liver cancer stem cells through the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway

Curcumin inhibits the growth of liver cancer stem cells through the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway

Curcumin ameliorates insulin signalling pathway in brain of Alzheimer’s disease transgenic mice

Inhibitors of dihydroceramide desaturase 1: Therapeutic agents and pharmacological tools to decipher the role of dihydroceramides in cell biology

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