Curcumin inhibits the growth of liver cancer by impairing myeloid‑derived suppressor cells in murine tumor tissues

Abstract

Curcumin, one of the active ingredients of Curcuma longa (Jianghuang), has been reported to exert multiple bioactivities, including pro-apoptotic and anti-inflammatory activities. In recent years, curcumin has been extensively studied, and it has been revealed that curcumin inhibits the growth of numerous types of cancer. However, to the best of our knowledge, the inhibitory effects of curcumin on the activation or expansion of myeloid-derived suppressor cells (MDSCs) in liver cancer and the underlying mechanism have not yet been determined. Therefore, the present study aimed to investigate the inhibitory effect of curcumin on MDSC activity and the associated anti-neoplastic mechanism in a HepG2 ×enograft mouse model. The effect of curcumin on the viability of Huh-7, MHCC-97H and HepG2 cells in vitro was analyzed using a Cell Counting Kit-8 assay. The effects of curcumin on tumor growth, numbers of MDSCs, expression levels of proteins involved in the toll-like receptor 4 (TLR4)/NF-κB signaling pathway, levels of related inflammatory factors and angiogenesis were determined in HepG2 ×enograft model mice, which were given different doses of curcumin via intragastrical administration. The results of the present study revealed that curcumin inhibited the viability of Huh-7, MHCC-97H and HepG2 cells and the growth of HepG2 ×enograft tumors in mice. Flow cytometric analysis indicated that curcumin reduced the number of MDSCs in mouse xenograft tumors. In addition, the results demonstrated that curcumin inhibited the TLR4/NF-κB signaling pathway and the expression of inflammatory factors, including IL-6, IL-1β, prostaglandin E2 and cyclooxygenase-2, in mouse xenograft tumors. Furthermore, curcumin suppressed the secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-colony stimulating factor (G-CSF), which are essential factors for MDSCs modulation, in tumor tissues. Additionally, curcumin was revealed to inhibit angiogenesis, which was demonstrated by the downregulation of the expression levels of vascular endothelial growth factor, CD31 and α-smooth muscle actin in western blotting, immunohistochemistry and immunofluorescence experiments. In conclusion, the findings of the present study identified a novel mechanism via which curcumin may suppress the growth of liver cancer by reducing the numbers of MDSCs and subsequently disrupting the process of angiogenesis. These conclusions were supported by the observed inactivation of the TLR4/NF-κB signaling pathway-mediated inflammatory response and the downregulation of GM-CSF and G-CSF secretion in xenograft tissues.

Curcumin Reverses NNMT-Induced 5-Fluorouracil Resistance via Increasing ROS and Cell Cycle Arrest in Colorectal Cancer Cells

“…We used 30 mg/kg 5-FU every 2 days for the 5-FU chemotherapy groups, as described in our previous study [ 7 ]. A previous study reported that up to 240 mg/kg/day is considered safe for mice [ 25 ]. In the current study, we used 100 mg/kg/day Cur for the 5-FU combination groups.…”

Frankincense myrrh attenuates hepatocellular carcinoma by regulating tumor blood vessel development through multiple epidermal growth factor receptor-mediated signaling pathways

“…The mice in the control groups were given saline at a volume equal to the treatment volume. The intervention was maintained for 14 d; the mouse body and tumor weights were regularly measured (every three days), and the tumor volume was calculated (tumor volume = length × width 2 /2)[ 25 , 26 ]. At the end of the intervention, the mice were euthanized, and the tumor tissues were removed from the mice.…”

Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy

“…Curcumin also inhibited the growth of liver cancer in vivo and in vitro via diminished expression of inflammatory factors, such as cyclooxygenase-2 (COX-2), prostaglandin E2, IL-1β, and IL-6, as well as inhibition of the TLR4/NF-κB signaling pathway. Moreover, curcumin reduced VEGF, granulocyte-colony-stimulating factor (G-CSF), and granulocyte−macrophage colony-stimulating factor (GM-CSF) ( 88 ). Additionally, curcumin decreased the migration and proliferation of non-small-cell lung cancer cell (NSCLC) cells via interfering with EGFR and TLR4/MyD88 pathways and increasing cell cycle arrest in the G2/M phase ( 89 ).…”