licochalcone-a and Colorectal-Neoplasms

Bazhen Decoction (BZD) is a common adjuvant therapy drug for colorectal cancer (CRC), although its anti-tumor mechanism is unknown. This study aims to explore the core components, key targets, and potential mechanisms of BZD treatment for CRC.. The Traditional Chinese Medicine Systems Pharmacology (TCMSP) was employed to acquire the BZD's active ingredient and targets. Meanwhile, the Drugbank, Therapeutic Target Database (TTD), DisGeNET, and GeneCards databases were used to retrieve pertinent targets for CRC. The Venn plot was used to obtain intersection targets. Cytoscape software was used to construct an "herb-ingredient-target" network and identify core targets. GO and KEGG pathway enrichment analyses were conducted using R language software. Molecular docking of key ingredients and core targets of drugs was accomplished using PyMol and Autodock Vina software. Cell and animal research confirmed Bazhen Decoction efficacy and mechanism in treating colorectal cancer.. BZD comprises 173 effective active ingredients. Using four databases, 761 targets related to CRC were identified. The intersection of BZD and CRC yielded 98 targets, which were utilized to construct the "herb-ingredient-target" network. The four key effector components with the most targets were quercetin, kaempferol, licochalcone A, and naringenin. Protein-protein interaction (PPI) analysis revealed that the core targets of BZD in treating CRC were AKT1, MYC, CASP3, ESR1, EGFR, HIF-1A, VEGFR, JUN, INS, and STAT3. The findings from molecular docking suggest that the core ingredient exhibits favorable binding potential with the core target. Furthermore, the GO and KEGG enrichment analysis demonstrates that BZD can modulate multiple signaling pathways related to CRC, like the T cell receptor, PI3K-Akt, apoptosis, P53, and VEGF signaling pathway.. BZD treats CRC through multiple components, targets, and metabolic pathways. BZD can reverse the abnormal expression of genes such as PI3K, AKT, MYC, EGFR, HIF-1A, VEGFR, JUN, STAT3, CASP3, and TP53, and suppresses the progression of colorectal cancer by regulating signaling pathways such as PI3K-AKT, P53, and VEGF. Furthermore, BZD can increase the number of T cells and promote T cell activation in tumor-bearing mice, enhancing the immune function against colorectal cancer. Among them, quercetin, kaempferol, licochalcone A, naringenin, and formaronetin are more highly predictive components related to the T cell activation in colorectal cancer mice. This study is of great significance for the development of novel anti-cancer drugs. It highlights the importance of network pharmacology-based approaches in studying complex traditional Chinese medicine formulations.

Topics: Animals; Caspase 3; CD8-Positive T-Lymphocytes; Colorectal Neoplasms; ErbB Receptors; Kaempferols; Mice; Molecular Docking Simulation; Network Pharmacology; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Quercetin; Tumor Suppressor Protein p53; Vascular Endothelial Growth Factor A

Hypoxic cellular proliferation is a common feature of tumor cells and is associated with tumor progression. Therefore, the inhibition of hypoxic cellular proliferation is expected to regulate malignancy processes. Licochalcone A (LicA) is known to show inhibitory effects on cell growth in normoxia, but it is unclear whether LicA exerts similar effects in hypoxia. Here, we studied the inhibitory activity of LicA in the hypoxic cellular proliferation of tumor cells and its molecular mechanism using human cell lines derived from various tumors including neuroblastoma and colorectal cancer. LicA inhibited cell growth at a 50% inhibitory concentration between 7.0 and 31.1 µM in hypoxia. LicA significantly suppressed hypoxic induction of tropomyosin receptor kinase B (

Topics: Brain-Derived Neurotrophic Factor; Cell Hypoxia; Chalcones; Colorectal Neoplasms; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Membrane Glycoproteins; Neoplasm Proteins; Neuroblastoma; Receptor, trkB

Licochalcone A (LCA) exhibited anticancer activity through modulating reactive oxygen species (ROS) levels in some cancer cells and has been evidenced to suppress colorectal cancer (CRC) formation and progression. However, whether LCA mediates the progression of CRC by regulating ROS production remains unclear. To address this, HCT-116 cells were treated with LCA, resulting in G0/G1 phase arrest, apoptosis, and high ROS generation, which were attenuated by N-acetyl-L-cysteine, a ROS inhibitor. In addition, LCA suppressed the expression of thioredoxin reductase 1 (TrxR1) in HCT-116 cells, leading to high ROS levels and apoptosis. Moreover, LCA administration combined with TrxR1 inhibition further enhanced the production of ROS and apoptosis in HCT-116 cells compared to LCA administration or TrxR1 inhibition alone. These results demonstrated that LCA might enhance the production of ROS by targeting TrxR1, leading to apoptosis in HCT-116 cells, which provides potential insight for the interventional treatment of CRC.

Topics: Antineoplastic Agents; Apoptosis; Cell Cycle Checkpoints; Chalcones; Colorectal Neoplasms; HCT116 Cells; Humans; Reactive Oxygen Species; Signal Transduction; Thioredoxin Reductase 1

Licochalcone A (LicA), a major phenolic constituent of licorice, has antiproliferative and anti-inflammatory properties in human and murine cell lines. We previously showed that LicA down-regulates the expression of cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) via the modulation of nuclear factor-kappaB and activator protein-1 activation in cell culture. We therefore tested whether LicA inhibits carcinogenesis and metastasis in mouse models. To induce colon carcinogenesis, C57BL/6 mice were given a single intraperitoneal injection of azoxymethane (10 mg/kg body weight), followed by 1% dextran sulfate sodium in the drinking water. Additionally, we also assessed the effect of LicA on liver metastasis by intrasplenic injection of BALB/c mice with CT-26 cells. Feeding the mice with LicA (5, 15, and 30 mg/kg body weight) significantly reduced tumor formation as well as the number of cells expressing proliferating cell nuclear antigen, beta-catenin, COX-2, and iNOS in the colon. LicA also decreased colon levels of proinflammatory cytokines and chemokines. In addition, LicA significantly increases survival of animals and inhibited liver metastasis as well as the expression of matrix metalloproteinase-9 in the liver. These preclinical studies indicate that LicA has potent antitumor and antimetastatic activity, suggesting that LicA could increase efficacy and improve patient outcomes in colorectal cancer.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Chalcones; Colorectal Neoplasms; Cytokines; Liver Neoplasms; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL