galangin and Liver-Neoplasms

Hepatocellular carcinoma (HCC) is one of the most common cancers and has a high mortality rate in less developed countries, especially in China. Galangin (GA), one of the most important and naturally active flavonoids, extracted primarily from the root of Alpinia officinarum Hance, has been demonstrated to be effective in the treatment of HCC. It is a substance with defensive actions and a broad range of biological properties, including inhibitory effects on bacteria, fungi, viruses, the control of hypertension and diabetes, and chemoprevention of several cancers. Experiments have shown that GA prevents HCC through multiple anti-cancer mechanisms, anti-genotoxic activity against environmental and dietary carcinogens; anti-proliferative effects through reversal of the Warburg effect in HCC; arrest of the cell cycle in the G0/G1 phase; induction of apoptosis via stimulation of reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, and the mitochondrial-dependent apoptosis pathway; induction of autophagy; and inhibition of angiogenesis, metastasis, and multidrug resistance (MDR). In addition, synergistic effects with other chemotherapy drugs have been demonstrated. Therefore, this review is focused on the anti-HCC mechanisms of GA.

Topics: Animals; Apoptosis; Carcinoma, Hepatocellular; Chemoprevention; Flavonoids; Humans; Liver Neoplasms

Galangin has been extensively studied as the antitumor agent in various cancers. However, the effect of galangin in hepatocellular carcinoma (HCC) remains elusive.. Using RNA sequencing, the differential expression of lncRNA in human HCC cell line with highly metastatic potential (MHCC97H) cells treated with galangin was investigated. Furthermore, H19 expression pattern was also determined in MHCC97H cells following treatment with galangin. In addition, knockdown and overexpression of H19 was performed to analyze the effect of the expression pattern of H19 on cell apoptosis, cell cycle, migration, and invasion in HCC cells. Moreover, the in vivo effect of galangin on tumor development was also determined in nude mice. In order to analyze loss expression of H19 in vivo, clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) was used.. Total of 50 lncRNAs were significantly differentially expressed in MHCC97H cells treated with galangin. Besides, the expression of H19 was markedly reduced following treatment with galangin in MHCC97H cells. Compared to the Control group, the galangin-treated group inhibited cell migration and invasion. Knockdown of H19 expression showed increased cell apoptosis and decreased invasion. In addition, RNA-seq data also identified 161 mRNA which was significantly differentially expressed following treatment with galangin. To further determine the underlying mechanism, p53 protein was analyzed. Notably, the results indicated that knockdown of H19 and miR675 induced the expression of p53, eventually promoting cell apoptosis in MHCC97H cells. These results indicated that galangin promoted cell apoptosis through reduced the expression of H19 and miR675 in MHCC97H cells. The in vivo result showed that compared to the Con, tumor growth was remarkably suppressed with loss expression of H19.. Our data suggested that galangin has a crucial role in hepatocarcinogenesis through regulating the expression pattern of H19.

Topics: Animals; Apoptosis; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Movement; Flavonoids; Gene Expression; Humans; Liver Neoplasms; Mice; Mice, Nude; RNA, Long Noncoding; Transfection

Hepatocellular carcinoma (HCC) is the sixth most common cancer. The Warburg effect is an important way by which HCC adapts to a hypoxic environment. The aim of the present study was to determine whether and how galangin reverses the Warburg effect in HCC cells. We treated three HCC cell lines, HepG2, Hep3B and PLC/PRF/5 with galangin for 24h, respectively. Cell proliferation was measured with MTT assay. Glucose uptake, lactate production and the oxygen consumption were measured. Pyruvate kinase activities were detected by measuring the consumption of NADH, and glycolytic pathway-related proteins were measured by Western blotting. The results showed that galangin suppressed proliferation of HCC cells, decreased glucose absorption and lactate production of HCC. In addition, galangin also gave rise to increased oxygen consumption in all three HCC cell lines. After treatment with galangin, the activity of pyruvate kinase was up-regulated and the expression levels of glycolytic pathway-related proteins were changed. These results suggest that galangin suppresses the Warburg effect in HCC cells, indicating that galangin might be a potential therapeutic agent for HCC.

Topics: Aerobiosis; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Flavonoids; Glycolysis; Humans; Liver Neoplasms; Pyruvate Kinase; Up-Regulation

Galangin suppresses proliferation and induces apoptosis and autophagy in hepatocellular carcinoma (HCC) cells, but the precise mechanism is not clear. In this study, we demonstrated that galangin induced autophagy, enhanced the binding of SIRT1-LC3 and reduced the acetylation of endogenous LC3 in HepG2 cells. But this autophagy was inhibited by inactivation of SIRT1 meanwhile, galangin failed to reduce the acetylation of endogenous LC3 after SIRT1 was knocked-down. Collectively, these findings demonstrate a new mechanism by which galangin induces autophagy via the deacetylation of endogenous LC3 by SIRT1.

Topics: Acetylation; Autophagy; Carcinoma, Hepatocellular; Flavonoids; Hep G2 Cells; Humans; Liver Neoplasms; Microtubule-Associated Proteins; Models, Biological; Sirtuin 1; Up-Regulation

Galangin can suppress hepatocellular carcinoma (HCC) cell proliferation. In this study, we demonstrated that galangin induced autophagy by activating the transforming growth factor (TGF)-β receptor/Smad pathway and increased TGF-β receptor I (RI), TGF-βRII, Smad1, Smad2, Smad3 and Smad4 levels but decreased Smad6 and Smad7 levels. Autophagy induced by galangin appears to depend on the TGF-β receptor/Smad signalling pathway because the down-regulation of Smad4 by siRNA or inhibition of TGF-β receptor activation by LY2109761 blocked galangin-induced autophagy. The down-regulation of Beclin1, autophagy-related gene (ATG) 16L, ATG12 and ATG3 restored HepG2 cell proliferation and prevented galangin-induced apoptosis. Our findings indicate a novel mechanism for galangin-induced autophagy via activation of the TGF-β receptor/Smad pathway. The induction of autophagy thus reflects the anti-proliferation effect of galangin on HCC cells.

Topics: Antineoplastic Agents; Apoptosis; Apoptosis Regulatory Proteins; Autophagy; Carcinoma, Hepatocellular; Cell Proliferation; Dose-Response Relationship, Drug; Flavonoids; Hep G2 Cells; Humans; Liver Neoplasms; Protein Serine-Threonine Kinases; Pyrazoles; Pyrroles; Receptor, Transforming Growth Factor-beta Type I; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta; RNA Interference; Signal Transduction; Smad Proteins; Transfection; Transforming Growth Factor beta

Prolonged endoplasmic reticulum (ER) stress may activate apoptotic pathways in cancer cells. It is suggested that ER stress has the potential of enhancing tumor death in cancer therapy. Galangin, a flavonol derived from Alpinia officinarum Hance, has been shown to suppress the proliferation of hepatocellular carcinoma cells (HCC). The aim of this study was to determine whether galangin was able to induce ER stress in HepG2, Hep3B and PLC/PRF/5 cells. The proliferation of HCC was tested by MTT method. Intracellular Ca(2+) levels were measured with Fluo3-AM.The proteins levels of GRP94, GRP78 and CHOP were detected by Western blot. To further understand the anti-HCC mechanism of galangin, mitogen-activated protein kinases (MAPKs) were detected. The results showed that galangin treatment induced ER stress was evidenced by increased protein levels of GRP94, GRP78 and CHOP, as well as increased free cytosolic Ca(2+) concentration. ER stress inhibitor 4-PBA and CHOP siRNA blocked significantly galangin-induced ER in all three cell lines. Further experiments showed that MAPKs involved in ER stress induced by galangin. In summary, galangin is identified as a stimulator of ER stress to suppress the proliferation of HCC, and may be used as a potential anti-cancer agent.

Topics: Antineoplastic Agents; Butylamines; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Flavonoids; Heat-Shock Proteins; Hep G2 Cells; Humans; Liver Neoplasms; MAP Kinase Kinase 4; Membrane Glycoproteins; Mitogen-Activated Protein Kinases; Transcription Factor CHOP

To investigate the mechanism by which galangin, a polyphenolic compound derived from medicinal herbs, induces apoptosis of hepatocellular carcinoma (HCC) cells.. The 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay was used to measure cell viability. Apoptosis was evaluated by in situ uptake of propidium iodide and Hoechst 33258 and was then detected by fluorescence microscopy. Protein expressions were detected by Western blotting. To confirm the apoptotic pathway mediated by galangin, cells were transfected by bcl-2 gene to overexpress Bcl-2 or siRNA to down-regulate Bcl-2 expression.. Galangin (46.25-370.0 micromol/L) exerted an anti-proliferative effect, induced apoptosis, and decreased mitochondrial membrane potential in a dose and time-dependent manner. Treatment with galangin induced apoptosis by translocating the pro-apoptotic protein Bax to the mitochondria, which released apoptosis-inducing factor and cytochrome c into the cytosol. Overexpression of Bcl-2 attenuated galangin-induced HepG2 cell apoptosis, while decreasing Bcl-2 expression enhanced galangin-induced cell apoptosis.. Our data suggests that galangin mediates apoptosis through a mitochondrial pathway, and may be a potential chemotherapeutic drug for the treatment of HCC.

Topics: Apoptosis; Carcinoma, Hepatocellular; Cell Line, Tumor; Dose-Response Relationship, Drug; Flavonoids; Humans; Liver Neoplasms; Membrane Potential, Mitochondrial; Mitochondria; Mutagens; Proto-Oncogene Proteins c-bcl-2; Signal Transduction

To investigate apoptosis of BEL-7402 cells induced by Galangin.. Cytotoxicity and cell viability were assayed by MT methods. Morphologic assessment of apoptosis was performed by fluorescence microscope, cell cycle and mitochondrial membrane potential were analyzed by flow cytometry, Caspases Activities were detected by chromogenic substrate assay.. BEL-7402 cells treated with Galangin showed apparently cytotoxicity, IC50 of Galangin was 30.15 mg/L The growth curve showed that the ratio of growth decreased with the increasing of concentration of Galangin. The apoptosis appeared 24 hours after treated with 20-80 mg/L Galangin, morphologic changes included nuclear chromatin condensation and fluorescence strength was observed with fluorescence microscope. The activity of Caspase-9 attained to peak value at 6 h, while Caspase-6 activity was up to peak value at 12h and Caspase-3 activity attained to peak value at 18 h.. Galangin may induce BEL-7402 cells apoptosis by mitochondrial pathway.

Topics: Alpinia; Antineoplastic Agents; Apoptosis; Caspases; Cell Cycle; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Flavonoids; Flow Cytometry; Humans; Liver Neoplasms; Membrane Potential, Mitochondrial; Plants, Medicinal; Rhizome

The in vitro antiviral activity of galangin (3,5,7-trihydroxyflavone), the major antimicrobial compound isolated from the shoots of Helichrysum aureonitens, was investigated against herpes simplex virus type 1 (HSV-1), coxsackie B virus type 1 (Cox B1), adenovirus type 31 (Ad31) and reovirus. At concentrations ranging from 12-47 micrograms/ml galangin showed significant antiviral activity against HSV-1 and CoxB1, limited activity against reovirus, and no antiviral activity against Ad31.

Topics: Adenoviruses, Human; Animals; Antiviral Agents; Carcinoma, Hepatocellular; Cells, Cultured; Enterovirus B, Human; Flavonoids; Haplorhini; Herpesvirus 1, Human; Humans; Kidney; Liver Neoplasms; Mutagens; Plant Extracts; Plant Shoots; Plants, Medicinal; Reoviridae; South Africa; Tumor Cells, Cultured