Curcumin suppresses the proliferation and tumorigenicity of Cal27 by modulating cancer‐associated fibroblasts of TSCC

Abstract

Cancer‐associated fibroblasts (CAFs) are “activated” fibroblasts in the tumor microenvironment (TME) and play a vital role in all steps of cancer development. Increasing evidence focusing on the function of CAFs suggests that CAFs are candidate therapeutic targets and that drugs targeting the modification of CAFs would suppress tumor progression and be beneficial to tumor treatment and prevention. In the present study, we found that curcumin reversed the phenotype of CAFs to that of peri‐tumor fibroblast (PTF)‐like cells by downregulating the expression of α‐SMA (a special marker for CAFs) and inhibiting the secretion of pro‐carcinogenic cytokines, including transforming growth factor‐β1 (TGF‐β1), matrix metalloproteinases 2 (MMP2), and stromal cell‐derived factor‐1 (SDF‐1). We further demonstrated that the conditioned medium (CM) derived from CAFs promoted the proliferation of Cal27, and this effect was confirmed by the xenograft model. More importantly, we found that curcumin blocked the CAF‐mediated enhancement of Cal27 proliferation in vitro and in vivo. In conclusion, our data suggest that curcumin reverses cell phenotype from CAF to PTF‐like cells and suppresses the CAF‐mediated proliferation and tumorigenicity of Cal27 by inhibiting TSCC CAFs.

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

“…As a well-known natural product with excellent pharmacological function, antitumor activity of curcumin has been investigated against several sorts of cancer cells in different phases including in vitro, in vivo and clinical studies. Noteworthy, all of the experiments are in agreement with the fact that curcumin is a potential agent in cancer therapy [30,45]. Curcumin can impair both proliferation and metastasis of cancer cells via inducing cell cycle arrest, triggering cytoskeletal remodeling and inhibiting epithelial-to-mesenchymal transition (EMT).…”

“…The first discovered pharmacological activity of curcumin is an antibacterial effect, found in 1949 [ 29 ]. Further studies focused on revealing other therapeutic and biological activities of curcumin including antiproliferative [ 30 ], antimetastatic [ 31 ], antioxidant [ 32 ], anti-inflammatory [ 33 ], antidiabetic [ 34 ], antiangiogenic [ 35 ], immunomodulatory [ 36 ], antitumor [ 37 ], antiatherosclerotic [ 38 ] and a lipid lowering effect [ 39 ] and regulating blood pressure [ 40 ].…”

Targeting the tumor immune microenvironment with “nutraceuticals”: From bench to clinical trials

“…Tumor-promoting CAFs are also influenced by CUR (10 mM), which was found to restore normal peritumor fibroblasts by reducing the expression of protumorigenic molecules (MMP-2, SDF-1, and TGF-β1) and characteristic molecular markers of CAFs (Ba et al, 2020). Accordingly, cellular and soluble components of the tumor microenvironment appear to be affected by CUR administration, but it is particularly worth noting that CUR activity strongly requires contributions from the host's immune system to reach its antitumor potential (Figs.…”

PTEN, a Barrier for Proliferation and Metastasis of Gastric Cancer Cells: From Molecular Pathways to Targeting and Regulation

“…It has pharmacological activities for the amelioration of cardiovascular disorders [ 182 ], improving blood lipids [ 183 ], reducing the risk of diabetes development [ 184 , 185 ], and so on. However, among them, antitumor activity of curcumin is of importance, since curcumin has been able to suppress proliferation of cancer cells, induce apoptosis, and inhibit their migration [ 167 , 186 , 187 ]. Curcumin can negatively affect proliferation of GC cells via targeting PTEN signaling.…”