ABSTRACT
PURPOSE: Breast cancer is the most commonly diagnosed malignancy among women. Breast cancer cells may develop resistance to current chemotherapy, thus new chemotherapeutic agents are urgently needed. METHODS: A major number of drugs with anticancer activity have been isolated from plants. Herewith, we investigated for the first time the effect of N-(p-coumaroyl) serotonin (CS), isolated from Centaurea seed on a drug-resistant breast carcinoma (MCF-7) cells. Viability and proliferation of the cells were examined with trypan blue exclusion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Caspace-8, cell cycle, and CD24/CD44/CD56/ CD58/CD71/CD15 expression were tested with flow cytometry. RESULTS: Treatment with CS significantly reduced cell viability. Induction of cell death and cell cycle arrest was confirmed with flow cytometry. After treatment with CS, there was a dose-dependent decrease in CD24/CD44/CD58/CD71 expression, whereas there was no change in CD56 and CD15 expression. CONCLUSION: The treatment of breast cancer cells with CS may represent a novel therapeutic strategy and requires further investigation.
Subject(s)
Breast Neoplasms , Cell Cycle , Cell Proliferation , Serotonin , Apoptosis , Breast Neoplasms/pathology , Cell Cycle/drug effects , Cell Cycle Checkpoints , Cell Line, Tumor , Female , Humans , MCF-7 Cells , Serotonin/pharmacologyABSTRACT
PURPOSE: Lung cancer is among the leading causes of cancer-related cases and cancer-associated deaths. Tumor cells frequently acquire chemoresistance and, due to that, new therapies are always needed in the fight against cancer. Pharmaceutical plants continue to offer novel compounds as anticancer therapies. METHODS: We studied the action of N-p-coumaroyl-serotonin (CS), a natural compound from Centaurea seed and safflower on a lung adenocarcinoma cell line. Cytotoxic or antiproliferative effect was studied using the MTT assay. Cell cycle, caspase-8 activation, mitochondrial membrane potential (MMP) and expression of CD15/CD56/CD24/CD44/CD58/CD71 were studied by flow cytometry. RESULTS: CS exterted antiproliferative and cytotoxic activity, independent of mitochondrial membrane disruption. This compound caused S phase arrest and a decrease in the expression of CD24/CD44/CD58/CD71. CONCLUSION: This is the first report on the in vitro action of CS against lung cancer, necessitating further studies towards its use as a potential anticancer agent.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Cell Proliferation/drug effects , Lung Neoplasms/pathology , Serotonin/pharmacology , Cell Cycle/drug effects , Humans , Lung Neoplasms/drug therapy , Membrane Potential, Mitochondrial/drug effects , Reactive Oxygen Species/metabolism , Tumor Cells, CulturedABSTRACT
Glioblastoma is the most common and most malignant primary brain tumor with a median survival of 15 months. Moschamine is an indole alkaloid that has a serotoninergic and cyclooxygenase inhibitory effect. In this study, we sought to determine whether moschamine could exert cytotoxic and cytostatic effects on glioma cells in vitro. Moschamine was tested for toxicity in zebrafish. We investigated the effect of moschamine on U251MG and T98G glioblastoma cell lines. Viability and proliferation of the cells were examined with trypan blue exclusion assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the xCELLigence system. Apoptosis (annexin-propidium iodide), cell cycle, and CD24/CD44/CD56/CD15 expression were tested with flow cytometry. Treatment with moschamine significantly reduced cell viability in both cell lines tested. Induction of cell death and cell cycle arrest was confirmed with flow cytometry in both cell lines. After treatment with moschamine, there was a dose-dependent decrease in CD24 and CD44 expression, whereas there was no change in CD56 and CD15 expression in T98G cell line. The zebrafish mortality on the fifth post-fertilization day was zero even for 1 mM of moschamine concentration. The treatment of glioblastoma cell lines with moschamine may represent a novel strategy for targeting glioblastoma.
Subject(s)
Apoptosis/drug effects , Cell Cycle Checkpoints/drug effects , Glioblastoma/drug therapy , Neoplasm Proteins/biosynthesis , Animals , CD24 Antigen/biosynthesis , CD56 Antigen/biosynthesis , Cell Line, Tumor , Cell Proliferation/drug effects , Disease Models, Animal , Gene Expression Regulation, Neoplastic/drug effects , Glioblastoma/pathology , Humans , Hyaluronan Receptors/biosynthesis , Lewis X Antigen/biosynthesis , ZebrafishABSTRACT
Glioblastoma is the most common and most malignant primary brain tumor with a median survival of 15 months. N-(p-coumaroyl) serotonin (CS) is an indole alkaloid with antioxidant, cardioprotective effects after ischemia and antitumor activity. In the present study we sought to determine whether could exert cytotoxic and cytostatic effects in glioma cells in vitro. CS was tested for toxicity in zebrafish. We investigated the effect of CS in U251MG and T98G glioblastoma cell lines. Viability and proliferation of the cells were examined with trypan blue exclusion assay and the xCELLigence system. Cell cycle, activation of caspase-8, mitochondrial membrane potential and CD24/CD44/CD56/CD15/CD71 expression were tested with flow cytometry. Treatment with CS significantly reduced cell viability in both cell lines tested. Induction of cell death and cell cycle arrest at G2/M and S-phase was confirmed with flow cytometry in both cell lines. CS produced significant higher activity of caspase-8 compared to control. After treatment with CS there was a dose-dependent increase in CD15 and CD71 expression, whereas there was no change in CD24/CD44/CD56 expression in both cell lines. The zebrafish mortality on the fifth post fertilization day was zero for even 1 mM of CS concentration. The treatment of glioblastoma cell lines with CS may represent a novel strategy for targeting glioblastoma. Further studies are obviously needed to elucidate the complete mechanism of its antitumor activity.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Brain Neoplasms/pathology , Cell Cycle Checkpoints/drug effects , Glioblastoma/pathology , Serotonin/pharmacology , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Evaluation, Preclinical , Humans , ZebrafishABSTRACT
The present phytochemical investigation of the seeds of Centaurea vlachorum led to the isolation and characterisation of four compounds including two indole alkaloids N-(p-coumaroyl) serotonin (1) and moschamine (2) and two dibenzylbutyrolactone lignans matairesinol (3) and arctiin (4). This is the first report on the isolation of non-volatile secondary metabolites from C. vlachorum. The chemataxonomic significance of these compounds was summarised. Moreover, the isolated compounds were tested for their free radical scavenging activity using the following in vitro assays: (i) interaction with the free stable radical of DPPH (1,1-diphenyl-2-picrylhydrazyl), (ii) inhibition of linoleic acid peroxidation with the dihydrochloric acid of 2,2-Azobis-2-amidinopropane (AAPH). Finally, their inhibitory activity towards soybean lipoxygenase was evaluated, using linoleic acid as substrate.