Cardamonin suppressed the migration, invasion, epithelial mesenchymal transition (EMT) and lung metastasis of colorectal cancer cells by down-regulating ADRB2 expression

Abstract

Context Cardamonin (CDN) can suppress cell growth in colorectal cancer (CRC), a common digestive malignancy. Objective We explored the effect and mechanism of CDN on metastatic CRC. Materials and methods Two cell lines (HT29 and HCT116) were initially treated with CDN at different concentrations (5, 10 and 20 μmol/L) or 50 μmol/L propranolol (positive control) for 24 or 48 h. Then, the two cell lines were separately transfected with siADRB2 and ADRB2 overexpression plasmids, and further treated with 10 μmol/L CDN for 24 h. The cell viability, migration and invasion were determined by cell counting kit-8 (CCK-8), wound healing and transwell assays, respectively. The levels of ADRB2, matrix metalloprotease (MMP)-2, MMP-9, E-cadherin and N-cadherin were measured by Western blotting or/and RT-qPCR. A CRC metastasis model was established to evaluate the antimetastatic potential of CDN (25 mg/kg). Results ADRB2 (3.2-fold change; p < 0.001) was highly expressed in CRC tissues. CDN at 10 μmol/L suppressed viability (69% and 70%), migration (33% and 66%), invasion (43% and 72%) and ADRB2 expression (2.2- and 2.84-fold change) in HT29 and HCT116 cells ( p < 0.001). CDN at 10 μmol/L inhibited MMP-2, MMP-9 and N-cadherin expression but promoted E-cadherin expression in CRC cells ( p < 0.001). Importantly, the effect of CDN on CRC cells was impaired by ADRB2 overexpression, but further enhanced by ADRB2 down-regulation ( p < 0.01). Additionally, ADRB2 overexpression reversed the inhibitory effect of CDN on metastatic lung nodules ( p < 0.05). Discussion and conclusions: CDN is a potential candidate for the treatment of metastatic CRC in clinical practice.

Chalcones and Gastrointestinal Cancers: Experimental Evidence

“…Additionally, several other enzymes have been identified as targets for chalcones, including aurora kinases [ 116 , 117 ], cyclooxygenases (COXs), 5-lipoxygenase [ 96 , 118 ], hexokinases II [ 119 ], matrix metalloproteinases [ 120 , 121 ], various tyrosin kinases [ 122 , 123 ] and NO synthase [ 124 ].…”

Study on the Action Mechanism of the Yifei Jianpi Tongfu Formula in Treatment of Colorectal Cancer Lung Metastasis Based on Network Analysis, Molecular Docking, and Experimental Validation

“…Subcutaneous xenograft experiments have demonstrated it to be highly tumorigenic. Therefore, it is currently widely used in the study of colorectal cancer metastasis [ 26 , 27 ].…”

Natural Chalcones and Derivatives in Colon Cancer: Pre-Clinical Challenges and the Promise of Chalcone-Based Nanoparticles

“…Furthermore, researchers investigated the molecular mechanism of CDN in inhibiting lung metastasis in CRC and its potential as a therapy for CRC patients [ 40 ]. They found that CDN effectively suppressed ADRB2 expression, leading to reduced viability, migration, invasion, and EMT in CRC cell lines (HT-29 and HCT116).…”

“…They found that CDN effectively suppressed ADRB2 expression, leading to reduced viability, migration, invasion, and EMT in CRC cell lines (HT-29 and HCT116). These in vitro findings were validated in a mouse metastasis model, highlighting CDN’s promise as a therapy for lung metastasis in CRC patients [ 40 ]. The study also revealed that EMT, a process that is crucial for cancer metastasis, involved the regulation of key markers such as E-cadherin, N-cadherin, MMP-2, and MMP-9, all of which were influenced by CDN treatment.…”