Synergistic effects of arsenic trioxide and silibinin on apoptosis and invasion in human glioblastoma U87MG cell line. 2012

Majid Zaki Dizaji, and Mohsen Malehmir, and Ardeshir Ghavamzadeh, and Kamran Alimoghaddam, and Seyed H Ghaffari
Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Patients with glioblastoma multiforme (GBM) have poor therapeutic outcomes despite their current therapy. In an attempt to increase the efficacy of therapy for GBM, we studied the efficacy of arsenic trioxide (ATO), a newly introduced treatment for glioma, combined with silibinin, a natural polyphenolic flavonoid, in the GBM cell line, U87MG. The combination therapy synergically inhibited metabolic activity, cell proliferation, and gelatinase A and B activities; it also increased apoptosis. Additionally, it decreased the mRNA level of cathepsin B, uPA, matrix metalloproteinase-2 and 9, membrane type 1-MMP, survivin, BCL2, CA9; it increased mRNA level of caspase-3. Altogether, these results showed that ATO and silibinin in some cases improved and/or complemented the anticancer effects. This study may supply insight into the design of new combination cancer therapies to cells intrinsically less sensitive to routine therapies and suggested a new combination therapy for the highly invasive human glioma treatment.

UI MeSH Term Description Entries
D009361 Neoplasm Invasiveness Ability of neoplasms to infiltrate and actively destroy surrounding tissue. Invasiveness, Neoplasm,Neoplasm Invasion,Invasion, Neoplasm
D010087 Oxides Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. Oxide
D001932 Brain Neoplasms Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. Brain Cancer,Brain Metastases,Brain Tumors,Cancer of Brain,Malignant Primary Brain Tumors,Neoplasms, Intracranial,Benign Neoplasms, Brain,Brain Neoplasm, Primary,Brain Neoplasms, Benign,Brain Neoplasms, Malignant,Brain Neoplasms, Malignant, Primary,Brain Neoplasms, Primary Malignant,Brain Tumor, Primary,Brain Tumor, Recurrent,Cancer of the Brain,Intracranial Neoplasms,Malignant Neoplasms, Brain,Malignant Primary Brain Neoplasms,Neoplasms, Brain,Neoplasms, Brain, Benign,Neoplasms, Brain, Malignant,Neoplasms, Brain, Primary,Primary Brain Neoplasms,Primary Malignant Brain Neoplasms,Primary Malignant Brain Tumors,Benign Brain Neoplasm,Benign Brain Neoplasms,Benign Neoplasm, Brain,Brain Benign Neoplasm,Brain Benign Neoplasms,Brain Cancers,Brain Malignant Neoplasm,Brain Malignant Neoplasms,Brain Metastase,Brain Neoplasm,Brain Neoplasm, Benign,Brain Neoplasm, Malignant,Brain Neoplasms, Primary,Brain Tumor,Brain Tumors, Recurrent,Cancer, Brain,Intracranial Neoplasm,Malignant Brain Neoplasm,Malignant Brain Neoplasms,Malignant Neoplasm, Brain,Neoplasm, Brain,Neoplasm, Intracranial,Primary Brain Neoplasm,Primary Brain Tumor,Primary Brain Tumors,Recurrent Brain Tumor,Recurrent Brain Tumors,Tumor, Brain
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D005909 Glioblastoma A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. Astrocytoma, Grade IV,Giant Cell Glioblastoma,Glioblastoma Multiforme,Astrocytomas, Grade IV,Giant Cell Glioblastomas,Glioblastoma, Giant Cell,Glioblastomas,Glioblastomas, Giant Cell,Grade IV Astrocytoma,Grade IV Astrocytomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077237 Arsenic Trioxide An inorganic compound with the chemical formula As2O3 that is used for the treatment of ACUTE PROMYELOCYTIC LEUKEMIA in patients who have relapsed from, or are resistant to, conventional drug therapy. Arsenic Oxide (As2O3),Arsenic Oxide (As4O6),Arsenic(III) Oxide,Arsenolite,Arsenous Anhydride,As2O3,As4O6,Diarsenic Trioxide,Naonobin,Tetra-Arsenic Hexaoxide,Tetra-Arsenic Oxide,Tetraarsenic Hexaoxide,Tetraarsenic Oxide,Trisenox,Trixenox,Tetra Arsenic Hexaoxide,Tetra Arsenic Oxide
D000077385 Silybin The major active component of silymarin flavonoids extracted from seeds of the MILK THISTLE, Silybum marianum; it is used in the treatment of HEPATITIS; LIVER CIRRHOSIS; and CHEMICAL AND DRUG INDUCED LIVER INJURY, and has antineoplastic activity; silybins A and B are diastereomers. 2,3-Dehydrosilybin,Alepa-forte,Ardeyhepan,Cefasilymarin,Durasilymarin,Hepa-Merz Sil,Hepa-loges,HepaBesch,Hepar-Pasc,Heparsyx,Heplant,Lagosa,Legalon Forte,Silibin,Silibinin,Silibinin A,Silibinin B,Silybin A,Silybin B,Silybinin,2,3 Dehydrosilybin,Alepa forte,Hepa Merz Sil,Hepa loges,Hepar Pasc
D001152 Arsenicals Inorganic or organic compounds that contain arsenic. Arsenic Compounds,Compounds, Arsenic
D012838 Silymarin A mixture of flavonoids extracted from seeds of the MILK THISTLE, Silybum marianum. It consists primarily of silybin and its isomers, silicristin and silidianin. Silymarin displays antioxidant and membrane stabilizing activity. It protects various tissues and organs against chemical injury, and shows potential as an antihepatoxic agent. Carsil,Karsil,Legalon,Silimarin

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