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

Abstract

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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Everolimus Reverses Palbociclib Resistance in ER+ Human Breast Cancer Cells by Inhibiting Phosphatidylinositol 3-Kinase(PI3K)/Akt/Mammalian Target of Rapamycin (mTOR) Pathway

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Zoledronic acid inhibits the growth of cancer stem cell derived from cervical cancer cell by attenuating their stemness phenotype and inducing apoptosis and cell cycle arrest through the Erk1/2 and Akt pathways

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