harmine and Stomach-Neoplasms

It has been reported that Harmine hydrochloride (HH) has an inhibitory effect on tumor cells, but the effect and mechanism of HH on gastric cancer cells remains unclear. The aim of this study was to investigate the effect and mechanism of HH on human gastric cancer cell line. In present study, results showed that HH could inhibit AGS, SGC7901 and HGC-27 cells in a time-dose-dependent manner (P < 0.01). Furthermore, this study demonstrated that more cells were arrested in G0/G1 phase, and apoptosis rate of AGS cells was significantly increased after HH treatment (P < 0.01). In addition, the study results showed that the mRNA and proteins of CyclinE, CyclinD1, PCNA declined dramatically, while p27, p21 increased significantly (P < 0.01). The results in this research also showed that the mRNA and proteins of Survivin and Bcl-2 decreased, while the expression of Bax, caspase-3, Bad increased significantly (P < 0.01). Also, the results of this study showed that invasion and migration of AGS cells decreased significantly after HH treatment (P < 0.01), with the expression of MMP-2, HIF-1 α and PRDX1 decreasing on observation after HH treatment (P < 0.01). In conclusion, HH has the property to inhibit GC cells via regulating GC cells' proliferation, apoptosis, invasion and migration.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Harmine; Humans; Stomach Neoplasms

Harmine, a β-carboline alkaloid from Peganum harmala, has multiple anti-tumor activities, especially for its folk therapy for digestive system neoplasm. However, the underlying mechanism of harmine on gastric cancer remains unclear.. To illuminate the potential anti-tumor activity and mechanism of harmine against gastric cancer cells.. The anti-proliferative activity of harmine in vitro was evaluated by MTT assay. The autophagic activity induced by harmine was assessed using GFP-LC3 transfection. FITC/PI double staining was applied for the apoptosis inspection. The mitochondrial membrane potential was detected by JC-1 fluorescence probe. The potential mechanisms for proteins level in autophagy and apoptosis were analyzed by Western blot.. Harmine exhibited potent effects on both autophagy and apoptosis. Treatment with harmine could enhance dots of GFP-LC3 in cells. Meanwhile, the process had connection with Beclin-1, LC3-II, and p62 by the inhibition of Akt/mTOR/p70S6K signaling. However, high concentration of harmine led to apoptosis characterized by the propidium/Annexin V-positive cell pollution, cell shrunk and the collapse of mitochondrial membrane potential. The regulation of Bcl-2, Bax and the gathering of cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 9 contributed to the induction of apoptosis. In addition, 10μM LY294002 (a specific inhibitor of PI3K/Akt) combination with 40μM harmine significantly increased the cytotoxicity to the gastric cancer cells and up-regulated both the apoptosis-related protein (cleaved-PARP, cleaved-caspase-3) and autophagy-related protein (Beclin-1, LC3-II, and p62). Adding the inhibitor of autophagy, 3-MA or BafA1, increased the viability of harmine-exposured gastric cancer cells, which confirmed the role of autophagy played in the gastric cancer cell death induced by harmine.. Harmine might be a potent inducer of apoptosis and autophagy, which offered evidences to therapy of harmine in gastric carcinoma in the folk medicine.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Apoptosis Regulatory Proteins; Autophagy; Beclin-1; Caspase 3; Caspase 9; Cell Line, Tumor; Drug Screening Assays, Antitumor; Harmine; Humans; Membrane Potential, Mitochondrial; Phosphatidylinositol 3-Kinases; Signal Transduction; Stomach Neoplasms

Cyclooxygenase-2 (COX-2) plays an important role in the carcinogenesis and progression of gastric cancer. Harmine is reported as a promising drug candidate for cancer therapy; however, effects and action mechanism of harmine on the human gastric cancer cells remain unclear. This study evaluated the anti-tumor effects of harmine on human gastric cancer both in vitro and in vivo. The cell proliferation was determined using MTT colorimetric assay. Apoptosis was measured by DAPI staining and flow cytometry analysis. The wound healing and transwell invasion assays were performed to evaluate the effects of harmine on the migration and invasion of gastric cancer cells. The expression of COX-2, proliferating cell nuclear antigen (PCNA), Bcl-2, Bax and matrix metalloproteinase-2 (MMP-2) was detected by Western blot analysis. Our results showed that harmine significantly inhibited cellular proliferation, migration, invasion and induced apoptosis in vitro, as well as inhibited tumor growth in vivo. In addition, harmine significantly inhibited the expression of COX-2, PCNA, Bcl-2 and MMP-2 as well as increased Bax expression in gastric cancer cells. These results collectively indicate that harmine induces apoptosis and inhibits proliferation, migration and invasion of human gastric cancer cells, which may be mediated by down-regulation of COX-2 expression.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; bcl-2-Associated X Protein; Cell Movement; Cell Proliferation; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Down-Regulation; Gastric Mucosa; Harmine; Humans; Male; Matrix Metalloproteinase 2; Mice; Mice, Nude; Peganum; Phytotherapy; Plant Extracts; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins c-bcl-2; Stomach; Stomach Neoplasms

Marine invertebrates harbour a wealth of micro-organisms in their bodies. Most of these micro-organisms can catabolize antibiotic compounds as chemical-defence compounds. These compounds not only play an important protective role for their producer and for their hosts, but also have high potential in medicinal applications. In order to discover natural anticancer products, 29 marine bacterial strains have been isolated from the sponge Hymeniacidon perleve, samples of which were collected from the intertidal zone during low tide off Nanji island in Eastern China. By means of a cytotoxicity bioassay, one strain, NJ6-3-1, with significant cytotoxic activity, was selected for culture in a 30-litre fermentation tank. The major cytotoxic compound in the metabolites of NJ6-3-1, separated by means of a bioassay-guided fractionation process, has been identified as norharman (a beta-carboline alkaloid) by electron-impact MS and NMR analyses. Norharman showed cytotoxicity towards both the HeLa cervical-cancer cell line and the BGC-823 stomach-cancer cell line, with an IC(50) of 5 microg/ml. Several methods were used to study the mechanism by which norharman is cytotoxic to HeLa cells. By means of an Acridine Orange/ethidium bromide dual-staining assay, condensation of chromatin was observed. A TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay showed degradation of DNA. Flow-cytometric analysis indicated that norharman could arrest cells at the G(2)/M phase of the cell cycle. These results demonstrate the cytotoxic mechanism of norharman involves the induction of apoptosis in HeLa cells.

Topics: Animals; Apoptosis; Biological Assay; Carbolines; Cell Line, Tumor; Drug Screening Assays, Antitumor; Female; Fermentation; Harmine; HeLa Cells; Humans; Molecular Structure; Porifera; Pseudoalteromonas; Stomach Neoplasms; Uterine Cervical Neoplasms

[corrected] To investigate the effect of apoptosis induced in human SGC-7901 cells by Harmine.. The effect of Harmine on human SGC-7901 cell survival and apoptosis was determined by MTT assay, light microscopy and flow cytometry. Cell genomic DNA was detected by agarose electrophoresis.. The survival of human SGC-7901 cells decreased; Apoptotic cells were observed by fluorescent microscope; FCM analysis showed that the peak of apoptosis increased. Typical DNA Ladder were detected in DNA agarose gel electrophoresis.. HM can induce apoptosis in human SGC-7901 cells.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Cell Survival; Flow Cytometry; Harmine; Humans; Peganum; Plants, Medicinal; Stomach Neoplasms

The carcinogenic effects of aniline and norharman given alone or in combination were examined in rats. Neoplastic changes including hyperplastic changes of the urinary bladder were not found in all groups. Papillomas of forestomach were observed in 5 rats out of 110 rats. However, this was not significantly different among the groups. Pyelonephritis or chronic nephritis were also seen in all groups. Hematological and blood biochemical analysis did not show any notable difference in the animals treated with aniline and/or norharman.

Topics: Alkaloids; Aniline Compounds; Animals; Carbolines; Carcinogens; Harmine; Kidney Diseases; Male; Papilloma; Pituitary Neoplasms; Rats; Stomach Neoplasms; Urinary Bladder Neoplasms