licochalcone-a and Carcinoma--Squamous-Cell

To investigate the effect of licochalcone A (LCA) on the proliferation and cell cycle of human lung squamous carcinoma cells and explore its possible molecular mechanism.. LCA is capable of inhibiting the proliferation and inducing cell cycle arrest in lung squamous carcinoma cells possibility by regulating the PI3K/Akt singling pathway.

Topics: Animals; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cell Cycle Checkpoints; Cyclin D1; Humans; Lung; Lung Neoplasms; Mice; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction

Lung squamous cell carcinoma (LSCC) is a highly heterogeneous malignancy with high mortality and few therapeutic options. Licochalcone A (LCA, PubChem ID: 5318998) is a chalcone extracted from licorice and possesses anticancer and anti‑inflammatory activities. The present study aimed to elucidate the anticancer effect of LCA on LSCC and explore the conceivable molecular mechanism. MTT assay revealed that LCA significantly inhibited the proliferation of LSCC cells with less cytotoxicity towards human bronchial epithelial cells. 5‑ethynyl‑2'‑deoxyuridine (EdU) assay demonstrated that LCA could reduce the proliferation rate of LSCC cells. The flow cytometric assays indicated that LCA increased the cell number of the G1 phase and induced the apoptosis of LSCC cells. LCA downregulated the protein expression of cyclin D1, cyclin E, CDK2 and CDK4. Meanwhile, LCA increased the expression level of Bax, cleaved poly(ADP‑ribose)polymerase‑1 (PARP1) and caspase 3, as well as downregulated the level of Bcl‑2. Proteomics assay demonstrated that LCA exerted its antitumor effects via inhibiting mitogen‑activated protein kinase (MAPK) signaling pathways and the expression of F‑box protein 5 (FBXO5). Western blot analysis showed that LCA decreased the expression of p‑ERK1/2, p‑p38MAPK and FBXO5. In the xenograft tumors of LSCC, LCA significantly inhibited the volumes and weight of tumors in nude mice with little toxicity in vital organs. Therefore, the present study demonstrated that LCA effectively inhibited cell proliferation and induced apoptosis

Topics: Animals; Apoptosis; Carcinoma, Squamous Cell; Cell Cycle Checkpoints; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Chalcones; F-Box Proteins; Humans; Lung; Lung Neoplasms; Mice; Mice, Nude; Mitogen-Activated Protein Kinases; Signal Transduction

We investigated Licochalcone-A (Lico-A)-induced apoptosis and the pathway underlying its activity in a pharyngeal squamous carcinoma FaDu cell line. Lico-A purified from root of Glycyrrhiza inflata had cytotoxic effects, significantly increasing cell death in FaDu cells. Using a cell viability assay, we determined that the IC50 value of Lico-A in FaDu cells was approximately 100 µM. Chromatin condensation was observed in FaDu cells treated with Lico-A for 24 h. Consistent with this finding, the number of apoptotic cells increased in a time-dependent manner when FaDu cells were treated with Lico-A. TRAIL was significantly up-regulated in Lico-A-treated FaDu cells in a dose-dependent manner. Apoptotic factors such as caspases and PARP were subsequently activated in a caspase-dependent manner. In addition, levels of pro-apoptotic factors increased significantly in response to Lico-A treatment, while levels of anti-apoptotic factors decreased. Lico-A-induced TRAIL expression was mediated in part by a MAPK signaling pathway involving ERK1/2 and p38. In xenograft mouse model, Lico-A treatment effectively suppressed the growth of FaDu cell xenografts by activating caspase-3, without affecting the body weight of mice. Taken together, these data suggest that Lico-A has potential chemopreventive effects and should therefore be developed as a chemotherapeutic agent for pharyngeal squamous carcinoma.

Topics: Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Squamous Cell; Caspase 3; Caspase 7; Cell Line, Tumor; Cell Survival; Chalcones; Chemoprevention; Glycyrrhiza; Head and Neck Neoplasms; Humans; Inhibitory Concentration 50; Keratinocytes; Male; Mice; Mice, Nude; Mitogen-Activated Protein Kinase 3; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Plant Extracts; Plant Roots; Signal Transduction; Squamous Cell Carcinoma of Head and Neck; TNF-Related Apoptosis-Inducing Ligand; Xenograft Model Antitumor Assays

The majority of anticancer drugs are of natural origin. However, it is unknown whether licochalcone A is cytotoxic towards oral squamous cell carcinoma (OSCC) cells. The goal of this study was to investigate the cytotoxic effects of licochalcone A on the human OSCC SCC-25 cells and to identify the underlying molecular mechanism. Exposure of SCC-25 cells to licochalcone A dose- and time-dependently decreased cell viability by arresting cell cycle at the S and G2/M phase as well as inducing apoptosis. Furthermore, the proapoptotic activity of licochalcone A was revealed by DNA fragmentation. Concomitantly, we observed activation of the effector caspases-3, induced by activation of the initiator caspases -8 and -9, which subsequent trigger both death receptor pathway and the mitochondrial apoptotic pathway in licochalcone A-mediated SCC-25 cell apoptosis. Besides, treatment with 50 μg/mL of licochalcone A for 36 h led to the cleavage of PARP, an indicator of apoptosis induction. Therefore licochalcone A may be a good candidate for development as a possible chemopreventive agent against OSCC.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Carcinoma, Squamous Cell; Caspase 3; Cell Line, Tumor; Cell Survival; Chalcones; G2 Phase; Humans; Mouth Neoplasms; Signal Transduction

Licochalcone A (LCA), a chalconoid derived from root of Glycyrrhiza inflata, has been known to possess a wide range of biological functions such as antitumor, anti-angiogenesis, antiparasitic, anti-oxidant, antibacterial and anti-inflammatory effects. However, the anticancer effects of LCA on oral squamous cell carcinoma (OSCC) have not been reported. Our data showed that LCA inhibited OSCC cell (HN22 and HSC4) growth in a concentration- and time-dependent manner. Mechanistically, it was mediated via downregulation of specificity protein 1 (Sp1) expression and subsequent regulation of Sp1 downstream proteins such as p27, p21, cyclin D1, Mcl-1 and survivin. Here, we found that LCA caused apoptotic cell death in HSC4 and HN22 cells, as characterized by sub-G1 population, nuclear condensation, Annexin V staining, and multi-caspase activity and apoptotic regulatory proteins such as Bax, Bid, Bcl(-xl), caspase-3 and PARP. Consequently, this study strongly suggests that LCA induces apoptotic cell death of OSCC cells via downregulation of Sp1 expression, prompting its potential use for the treatment of human OSCC.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Apoptosis Regulatory Proteins; Blotting, Western; Carcinoma, Squamous Cell; Cell Line, Tumor; Chalcones; Glycyrrhiza; Humans; Mouth Neoplasms; Phytotherapy; Plant Extracts; Plant Roots; Reverse Transcriptase Polymerase Chain Reaction; Sp1 Transcription Factor