Curcumin inhibits liver cancer by inhibiting DAMP molecule HSP70 and TLR4 signaling

Abstract

Curcumin has been revealed to inhibit liver cancer, however, no studies have reported that the mechanism of curcumin's action on liver cancer is related to damage-associated molecular pattern (DAMP) molecules heat shock protein 70 (HSP70) and the toll-like receptor 4 (TLR4) signaling. This study aimed to investigate whether the activation of TLR4 signaling by HSP70 could be inhibited by curcumin, thus investigating the possible mechanism of curcumin in the inhibition of liver cancer. Western blotting was used to evaluate the expression of the HSP70 and TLR4 in HepG2 cells and ELISA was used to detect the concentration of HSP70 in cell culture medium. A thermal tolerance HepG2 (HepG2TT) cell model was established to simulate HSP70 accumulation in the microenvironment. A certain concentration of curcumin was co-cultured with HepG2 and HepG2TT cells to observe the changes of HSP70 and TLR4. Our results revealed that heat stress significantly increased the expression of extracellular HSP70 (eHSP70) and TLR4 (P<0.01), but significantly reduced the expression of intracellular HSP70 (P<0.01). Curcumin inhibited proliferation, invasion, and metastasis of HepG2 cells, caused cells to remain in the DNA S phase, promoted apoptosis, and significantly reduced intracellular HSP70, eHSP70 and TLR4 levels of HepG2TT cells. Following the removal of curcumin, eHSP70 increased again. In summary, our results demonstrated that the antitumor effect of curcumin was related to the inhibition HSP70-TLR4 signaling.

The Cancer Prevention, Anti-Inflammatory and Anti-Oxidation of Bioactive Phytochemicals Targeting the TLR4 Signaling Pathway

“…Curcumin administration can reduce activation of microglia/macrophages and neuronal apoptosis through a mechanism involving the TLR4/MyD88/NF-κB signaling in experimental traumatic brain injury [ 70 ]. Recently, a study has shown that curcumin inhibits DAMP molecule HSP70 and TLR4 signaling in liver cancer cells [ 72 ].…”

LncRNA ZFPM2-AS1 Promotes Metastasis and Epithelial-mesenchymal Transition of Hepatocellular Carcinoma via Targeting miR-3612/ADAM15 Axis

“…Finally, we disclosed that curcumin, an active component of turmeric, displays various pharmacological activities [32]. The promising role of curcumin against different diseases is widely publicized [33].…”

Involvement of TLR4 in the protective effect of intra-articular administration of curcumin on rat experimental osteoarthritis

“…And activation of TLR4 would trigger inflammatory and catabolic responses by chondrocytes, thus is closely involved in OA-related cartilage damage 13 . The main aim of our study was to determine whether the TLR4 inhibitory activity of curcumin, which has been demonstrated in other pathological conditions such as liver cancer 15 , traumatic brain injury 16 and atherosclerosis 17 , contributed to its protective anti-inflammatory effect of curcumin on OA. And LPS, a canonical TLR4 activator, was used as a tool to up-regulate TLR4 in the joints.…”

“…Up to date, the TLR4 inhibitory activity of curcumin has been demonstrated in liver cancer HepG2 cells 15 , experimental traumatic brain injury 16 , and apolipoprotein E-knockout mice 17 etc. , which has been believed as a key underlying mechanism of curcumin’s anti-inflammatory properties.…”