galangin and Carcinoma--Squamous-Cell

Laryngeal cancers are mostly squamous cell carcinomas. Although targeting radio-resistant cancer cells is important for improving the treatmental efficiency, the signaling pathway- and therapeutic strategy-related to laryngeal carcinoma still require further study. Galangin is an active pharmacological ingredient, isolated from propolis and Alpinia officinarum Hance, and has been reported to have anticancer and anti-oxidative properties through regulation of cell cycle, resulting in angiogenesis, apoptosis, invasion and migration without triggering any toxicity in normal cells. PI3K/AKT and p38 are important signaling pathways to modulate cancer cell apoptosis and proliferation through caspase-3, NF-κB and mTOR signal pathways. Autophagy is also enhanced by activating LC3s and Beclin 1. In the present study, galangin was found to suppress laryngeal cancer cell proliferation. Also, flow cytometry, immunohistochemical and western blot analysis indicated that cell apoptosis was induced for galangin administration, promoting caspase-3 expression through regulating PI3K/AKT/NF-κB. Furthermore, galangin inhibited laryngeal cancer cell proliferation, related to p38 inactivation by galangin treatment. Additionally, mTOR activation regulated by PI3K/AKT was reduced by galangin, suppressing cancer cell transcription and proliferation. Our data also indicated that the tumor volume and weight in nude mice were reduced for galangin use in vivo accompanied by Ki-67 decrease and TUNEL increase in tumor tissues. Together, our data indicated that galangin has a potential role in suppressing human laryngeal cancer via inhibiting tumor cell proliferation, activating apoptosis and autophagy, which were regulated by p38 and AKT/NF-κB/mTOR pathways, providing a therapeutic strategy for human laryngeal cancer treatment.

Topics: Animals; Apoptosis; Carcinoma, Squamous Cell; Caspase 3; Cell Proliferation; Flavonoids; Flow Cytometry; Gene Expression Regulation, Neoplastic; Humans; Laryngeal Neoplasms; Mice; NF-kappa B; Oncogene Protein v-akt; Phosphatidylinositol 3-Kinases; Propolis; Signal Transduction; TOR Serine-Threonine Kinases; Xenograft Model Antitumor Assays

Galangin is an active pharmacological ingredient from propolis and Alpinia officinarum Hance, and has been reported to have anti-cancer and antioxidative properties. Berberine, a major component of Berberis vulgaris extract, exhibits potent anti-cancer activities through distinct molecular mechanisms. However, the anticancer effect of galangin in combination with berberine is still unknown. In the present study, we demonstrated that the combination of galangin with berberine synergistically resulted in cell growth inhibition, apoptosis and cell cycle arrest at G2/M phase with the increased intracellular reactive oxygen species (ROS) levels in oesophageal carcinoma cells. Pretreatment with ROS scavenger promoted the apoptosis dramatically induced by co-treatment with galangin and berberine. Treatment with galangin and berberine alone caused the decreased expressions of Wnt3a and β-catenin. Interestingly, combination of galangin with berberine could further suppress Wnt3a and β-catenin expression and induce apoptosis in cancer cells. Additionally, in nude mice with xenograft tumors, the combinational treatment of galangin and berberine significantly inhibited the tumor growth without obvious toxicity. Overall, galangin in combination with berberine presented outstanding synergistic anticancer role in vitro and in vivo, indicating that the beneficial combination of galangin and berberine might provide a promising treatment for patients with oesophageal carcinoma.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Berberine; beta Catenin; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Drug Synergism; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Flavonoids; G2 Phase Cell Cycle Checkpoints; Humans; Male; Mice, Inbred BALB C; Mice, Nude; Oxidative Stress; Reactive Oxygen Species; RNA Interference; Time Factors; Transfection; Tumor Burden; Wnt Signaling Pathway; Wnt3A Protein; Xenograft Model Antitumor Assays

Galangin, an active flavonoid component extracted from the propolis and root of Alpinia officinarum Hance, has anti-tumor activity, but the mechanisms by which galangin affects various cancers, including human head and neck squamous cell carcinoma (HNSCC) remain unclear. In this study, we demonstrated for the first time that galangin suppressed the growth of HNSCC in vivo. With the cell culture system, galangin inhibited the proliferation and colony formation of HNSCC cells in a dose-dependent manner. Galangin induced significant cell cycle arrest of the tumor cells at the G0/G1 phase, which was accompanied by reduced AKT phosphorylation and mammalian target of rapamycin and S6 kinase activation. Decreased expression of cyclin D1, cyclin-dependent kinase (CDK)4, CDK6 and phosphorylation of retinoblastoma protein was observed in galangin-treated HNSCC cells. In addition, galangin induced apoptosis of HNSCC cells, downregulating antiapoptotic protein Bcl-2 and Bcl-xL and upregulating proapoptotic protein Bax and cleaved caspase 3. Immunohistochemical analysis showed a dose-dependent reduction in cyclin-D1-positive cancer cells and an increase in TUNEL-positive cancer cells in galangin-administrated mouse tumor sections. Therefore, galangin may be a novel therapeutic option in human HNSCC treatment.

Topics: Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Squamous Cell; Cell Line, Tumor; Cyclin D1; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Cyclin-Dependent Kinase Inhibitor p21; Flavonoids; G1 Phase Cell Cycle Checkpoints; Head and Neck Neoplasms; Humans; Male; Mice; Mice, Inbred BALB C; Protein Kinase Inhibitors; Retinoblastoma Protein; Xenograft Model Antitumor Assays