licochalcone-a and Bone-Neoplasms

Because of the abnormal upregulation of matrix metalloproteinase (MMP) activities in tumors, MMP inhibitors (MMPIs) are validated anticancer drug candidates. We identified several MMPIs including mangiferin as an MMP-9 inhibitor with a half maximal inhibitory concentration (IC

Topics: Animals; Antineoplastic Agents; Biological Products; Bone Neoplasms; Matrix Metalloproteinase 13; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Mice; Molecular Docking Simulation; Osteosarcoma; Peptides

Licochalcone A (LicA) is isolated from the roots of. Cell viability was measured by MTT assay. Apoptosis and mitochondrial dysfunction were detected with Annexin V/PI staining and JC-1 staining by flow cytometry. The expressions of caspase- or mitochondrial-related proteins were demonstrated by western blotting. Antitumor effect of LicA on 143B xenograft mice in vivo.. These findings demonstrate that LicA has antitumor activities against human osteosarcoma cells through p38MAPK regulation of mitochondria-mediated intrinsic apoptotic pathways in vitro and in vivo.

Topics: Animals; Antineoplastic Agents, Phytogenic; Bone Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chalcones; Gene Expression Regulation, Neoplastic; Humans; MAP Kinase Signaling System; Membrane Potential, Mitochondrial; Mice; Mitochondria; Osteosarcoma; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Xenograft Model Antitumor Assays

The aim of this study was to determine whether the ethanol extract of roasted licorice (rLE) could inhibit breast cancer-mediated bone destruction. rLE treatment reduced the viability of MDA-MB-231 human metastatic breast cancer cells but did not show any cytotoxicity in hFOB1.19 human osteoblastic cells and murine bone marrow-derived macrophages (BMMs). rLE inhibited expression and secretion of receptor activator of nuclear factor κB ligand (RANKL) as well as the mRNA and protein expression of cyclooxygenase-2 in osteoblastic cells exposed to the conditioned medium of breast cancer cells. rLE dramatically inhibited RANKL-induced osteoclastogenesis in BMMs, thereby reducing osteoclast-mediated pit formation. Moreover, treatment with licochalcone A and isoliquiritigenin as the active components, whose contents are increased by the roasting process, remarkably suppressed RANKL-induced osteoclast formation in BMMs, respectively. Furthermore, orally administered rLE substantially blocked tumor growth and bone destruction in mice inoculated with breast cancer cells in the tibiae. Serum levels of tartrate-resistant acid phosphatase and C-terminal cross-linking telopeptide of type I collagen and trabecular bone morphometric parameters were reversed to almost the same levels as the control mice by the rLE treatment. In conclusion, rLE may be a beneficial agent for preventing and treating bone destruction in patients with breast cancer.

Topics: Acid Phosphatase; Animals; Bone and Bones; Bone Neoplasms; Bone Resorption; Breast Neoplasms; Cell Line, Tumor; Chalcones; Cyclooxygenase 2; Female; Glycyrrhiza; Humans; Isoenzymes; Macrophages; Male; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Neoplasm Metastasis; Osteoblasts; Osteoclasts; Plant Extracts; RANK Ligand; Tartrate-Resistant Acid Phosphatase