Decursin inhibits tumor progression in head and neck squamous cell carcinoma by downregulating CXCR7 expressionin vitro

Abstract

CXC chemokine receptor 7 (CXCR7) is frequently overexpressed in cancer and plays a significant role in tumor growth and metastasis. Consequently, inhibition of CXCR7 is important for treatment strategies. However, little is known concerning the biological role of CXCR7 and its underlying mechanisms in head and neck squamous cell carcinoma (HNSCC). The present study investigated the role of CXCR7 in HNSCC, as well as the effects of decursin, a pyranocoumarin compound isolated from Angelica gigas Nakai, on CXCR7 and its downstream signaling. Expression levels of CXCR7 in HNSCC cells were examined using flow cytometry, reverse transcriptase PCR, western blot analysis, and immunofluorescence. The effects of CXCR7 on cell proliferation, migration, and invasion were studied using CCK-8, gap closure, and transwell assays. The results revealed that decursin significantly reduced CXCR7 expression and inhibited cell proliferation, migration, and invasion of human HNSCC cell lines. In addition, decursin induced G0/G1 cell cycle arrest in CXCR7-overexpressing cells and decreased the levels of cyclin A, cyclin E, and CDK2. Furthermore, CXCR7 promoted cancer progression via the STAT3/c-Myc pathway in HNSCC; suppression of CXCR7 with decursin prevented this effect. These results suggest that CXCR7 promotes cancer progression through the STAT3/c-Myc pathway and that the natural compound decursin targets CXCR7 and may be valuable in the treatment of HNSCC.

JI017 Induces Cell Autophagy and Apoptosis via Elevated Levels of Reactive Oxygen Species in Human Lung Cancer Cells

“…Furthermore, it is known that natural treatments for various inflammatory diseases and obesity have neuroprotective effects [39][40][41]. Decursin-inhibited tumor progression in head and neck squamous cell, as well as the active compound of Ag, induces apoptosis by inhibiting the PI3K-Akt axis in HeLa cells [42,43]. Among the active compounds of Zo, 6-gingerol suppresses tumor cell proliferation by blocking the nuclear translocation of HIF-1α in lung cancer [44].…”

A comprehensive review of the anticancer effects of decursin

“…Therefore, targeting cell cycle regulatory proteins to block cell growth provides a research direction for anticancer drug discovery. Decursin can inhibit the cell cycle at different checkpoints, blocking the G0/G1 and S phases of the cell cycle in the majority of cancers, with a small percentage of cancer cells being inhibited at the G2 phase ( Jiang et al, 2007 ; Oh et al, 2019 ; Joo et al, 2022 ). Decursin promotes G1 phase block in 253J and HCT116 cancer cells by enhancing P21 and downregulating cyclin D1 expression through activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase1/2 (MAPK/ERK1/2) signaling pathway ( Kim et al, 2010d ).…”

“…It also inhibits Janus kinase 2 (JAK2) to prevent the activation of the signal transducer and activator of transcription 3 (STAT3) ( Kim et al, 2011 ; Jang et al, 2013 ; Ke et al, 2018 ). In addition, in SNU-216, SNU-484, SNU-1041, and SNU-1076 cells of stomach cancer, decursin can also reduce c-myc expression by targeting STAT3 signals mediated by chemokine receptor 7 (CXCR7) to activate the caspase family to inhibit tumor growth and induce apoptosis ( Kim et al, 2019 ; Joo et al, 2022 ). Decursin also affects the abnormal activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway to influence cancer growth, metabolism, and survival.…”

“…Among them, decursin increased cell proliferation, growth, migration, and invasion in gastric cancer by downregulating CXCR7 to affect the STAT3/c-Myc pathway ( Kim et al, 2019 ). In addition, the specific mechanism of migration and invasion inhibition by decursin in head and neck squamous cell carcinoma (SNU-1041 and SNU-1076) and hepatocellular carcinoma (HepG2) is unclear and needs further insight to enable the natural product and its derivatives to play an important role in inhibiting the activity of MMP-2 and MMP-9 ( Li et al, 2018 ; Joo et al, 2022 ).…”

In Vitro Anticancer Activity of Mucoadhesive Oral Films Loaded with Usnea barbata (L.) F. H. Wigg Dry Acetone Extract, with Potential Applications in Oral Squamous Cell Carcinoma Complementary Therapy

“…Xia [ 16 ], Cynara cardunculus L. [ 17 ], Imperata cylindrica (L.) P.Beauv. [ 18 ], Caesalpinia sappan L. [ 19 ], Angelica gigas Nakai [ 20 ], Aloe barbadensis Miller [ 21 ], Padina gymnospora [ 22 ] and Usnea barbata (L.) F.H.Wigg [ 23 , 24 , 25 ]. The principal mechanism triggered in the OSCC tumor cell line is oxidative stress, which induces DNA damage and cell cycle arrest, leading to apoptotic cell death [ 16 , 17 , 23 , 24 ].…”