ENHANCED p53-DEPENDENT GROWTH INHIBITION OF HUMAN GLIOBLASTOMA CELLS BY COMBINATORIAL TREATMENT OF TEMOZOLOMIDE AND NOVEL PURIFIED NATURAL CARBOHYDRATE OF PLEUROTUS FLORIDA
01 Jun 2017-International Journal of Pharmacy and Pharmaceutical Sciences-Vol. 9, Iss: 6, pp 189-193
TL;DR: It confirms that Fr-II synergizes with TMZ to significantly intensify its anti-proliferative properties, thereby emerging as an effective element for combinatorial treatment of glioblastoma.
Abstract: Objective: This study was designed to analyze the combinatorial chemotherapeutic effect of temozolomide (TMZ), the most common drug in glioblastoma treatment and a purified carbohydrate (Fr-II) from the edible mushroom Pleurotus florida , on human glioblastoma cell lines Methods: Fr-II was purified by size-exclusion chromatography and characterised by different mass spectroscopy analysis Human glioblastoma cells were treated with TMZ, Fr-II, and combination of TMZ and Fr-II Cell cytotoxicity was measured by MTT assay, cell cycle phase distribution was determined by cell cycle analysis and followed by the relative p53 protein expression was analyzed by western blot analysis Results: Chemical analysis of Fr-II confirmed the glycosidically linked two units of glucose with terminally attached mannitol with mass of 506 Da Fr-II treatment exhibited cytotoxicity in both the cell lines in a dose-dependent manner with most effective dose at 200µg/ml When Fr-II (200µg/ml) was combined with a dose range of TMZ it showed a more cellular cytotoxicity compared to the cytotoxicity of TMZ alone with most oppressive combinatorial dose at 400µM (TMZ)+200µg/ml (Fr-II) In compliance, with the above results, both cell lines showed a 10% increase in no of cells (p<005) in G 2 /M phase indicating an arrest of cell cycle and increased p53 protein expression (p<005) at the combinatorial dose than TMZ alone at 400µM, but Fr-II alone didn’t show any cell cycle arrest nor did it show increased p53 expression Conclusion: Therefore it confirms that Fr-II synergizes with TMZ to significantly intensify its anti-proliferative properties, thereby emerging as an effective element for combinatorial treatment of glioblastoma
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TL;DR: The case of a 70-year-old gentleman who was referred to the Surgical Emergency Unit with signs and symptoms of large bowel obstruction on a background of long-standing constipation and a strong wish of the patient to avoid a stoma is presented.
5 citations
TL;DR: There are different environmental factors affecting the fruiting body development of mushrooms, and by adjusting various factors like temperature, light, media composition production of mushrooms can be increased.
Abstract: Objective: Fungi are heterotrophs and are involved in decomposition, nutrient cycling and nutrient transport, and are indispensable for achieving sustainable development. Mushrooms are the fungi with a distinctive fruiting body. Mushrooms are produced all over the world. In India, Punjab is the leading mushroom growing state. Mushrooms are rich sources of proteins, vitamins and minerals. Different types of immunoceuticals like lentinan, schizophyllan, active hexose correlated compound (AHCC) etc. have also been prepared from various mushrooms. The present review work highlights important observations in the area of mushroom. Methods: This review also shows that how several factors affect the fruiting body formation of mushrooms, which includes physiological (composition of culture media) and environmental factors (light, temperature, salinity, etc.). There are different factors like light, temperature etc. which affects the fruiting body development. Results: It has been found that, light has positive effects on hyphal aggregation and fruiting body maturation. It has been found that in oyster mushroom, light is essential for both normal expansion of pileus and in spore formation. It has been found that length of Stipe and the diameter of cap decreases with an increase in the concentration of CO 2. Also, there is a range of temperature within which sporophore development occurs. The composition of media affects the growth of mushrooms too. It’s important to maintain a balance between carbon and nitrogen sources for induction of the fruiting body. Conclusion: There are different environmental factors affecting the fruiting body development of mushrooms. Hence, by adjusting various factors like temperature, light, media composition production of mushrooms can be increased.
2 citations
TL;DR: Overproduction of ROS in rotenone-treated human GBM T98G cells could suppress the MnSOD protein level and activity even though mRNA synthesis has been increased.
Abstract: Objective: Glioma is the most common human primary brain tumor which is highly resistant to oxidative stress-based anticancer. The aim of this study was to analyze the effect of rotenone-induced reactive oxygen species (ROS) on the modulation of manganese superoxide dismutase (MnSOD) expression and cell viability in human glioblastoma (GBM) T98G cells. Methods: In this in vitro experimental study, T98G cells were treated with high-dose rotenone (0.5, 5, and 50 μM, respectively). Following rotenone treatment and intracellular ROS, both peroxide and superoxide radicals were determined. Moreover, we analyzed MnSOD mRNA expression, protein, and specific activity, as well as cell survival including viability, proliferation, apoptosis, and mitochondrial structure. Results: High-dose rotenone treatment of T98G cells significantly increased intracellular ROS and MnSOD mRNA, but its protein and specific activity definitely decreased. The treatment also led to a reduction of cell viability, enhancement of apoptosis, and disruption of mitochondrial integrity. Conclusion: Overproduction of ROS in rotenone-treated human GBM T98G cells could suppress the MnSOD protein level and activity even though mRNA synthesis has been increased. This modulation led to reduced survival of T98G cells through induction of cell death rather than inhibition of cell proliferation.
1 citations
References
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TL;DR: In this article, a method was developed to determine submicro amounts of sugars and related substances using a phenol-sulfuric acid reaction, which is useful for the determination of the composition of polysaccharides and their methyl derivatives.
Abstract: Simple sugars, oligosaccharides, polysaccharides, and their derivatives, including the methyl ethers with free or potentially free reducing groups, give an orangeyellow color w-hen treated with phenol and concentrated sulfuric acid. The reaction is sensitive and the color is stable. By use of this phenol-sulfuric acid reaction, a method has been developed to determine submicro amounts of sugars and related substances. In conjunction with paper partition chromatography the method is useful for the determination of the composition of polysaccharides and their methyl derivatives.
45,381 citations
"ENHANCED p53-DEPENDENT GROWTH INHIB..." refers methods in this paper
...Each fraction was monitored for the estimation of neutral carbohydrates using phenol-sulphuric acid assay method [25]....
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TL;DR: The p53 tumour-suppressor gene integrates numerous signals that control cell life and death, and the disruption of p53 has severe consequences when a highly connected node in the Internet breaks down.
Abstract: The p53 tumour-suppressor gene integrates numerous signals that control cell life and death. As when a highly connected node in the Internet breaks down, the disruption of p53 has severe consequences.
6,605 citations
TL;DR: Developments in the understanding of malignant brain tumours in the context of the evolving notion of molecular pathology are summarized and the implications that this work has on the design of new treatment regimens are discussed.
Abstract: Malignant brain tumours continue to be the cause of a disproportionate level of morbidity and mortality across a wide range of individuals. The most common variants in the adult and paediatric populations - malignant glioma and medulloblastoma, respectively - have been the subject of increasingly intensive research over the past two decades that has led to considerable advances in the understanding of their basic biology and pathogenesis. This Review summarizes these developments in the context of the evolving notion of molecular pathology and discusses the implications that this work has on the design of new treatment regimens.
694 citations
"ENHANCED p53-DEPENDENT GROWTH INHIB..." refers background in this paper
...Thus, there is an urgent need for more effective treatment strategies which would ensure better prognosis of patients with brain tumors [3]....
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TL;DR: Several small molecule inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1), a critical BER protein are yielding promising results clinically, both in combination with TMZ and as single agent chemotherapy in patients whose tumours possess homologous recombination DNA repair defects.
Abstract: Glioblastoma multiforme is the most common aggressive adult primary tumour of the central nervous system. Treatment includes surgery, radiotherapy and adjuvant temozolomide (TMZ) chemotherapy. TMZ is an alkylating agent prodrug, delivering a methyl group to purine bases of DNA (O6-guanine; N7-guanine and N3-adenine). The primary cytotoxic lesion, O6-methylguanine (O6-MeG) can be removed by methylguanine methyltransferase (MGMT; direct repair) in tumours expressing this protein, or tolerated in mismatch repair-deficient (MMR-) tumours. Thus MGMT or MMR deficiency confers resistance to TMZ. Inherent- and acquired resistance to TMZ present major obstacles to successful treatment. Strategies devised to thwart resistance and enhance response to TMZ, including inhibition of DNA repair mechanisms which contribute to TMZ resistance, are under clinical evaluation. Depletion of MGMT prior to alkylating agent chemotherapy prevents O6-MeG repair; thus, MGMT pseudosubstrates O6-benzylguanine and lomeguatrib are able to sensitise tumours to TMZ. Disruption of base excision repair (BER) results in persistence of potentially lethal N7- and N3- purine lesions contributing significantly to TMZ cytoxicity particularly when O6-MeG adducts are repaired or tolerated. Several small molecule inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1), a critical BER protein are yielding promising results clinically, both in combination with TMZ and as single agent chemotherapy in patients whose tumours possess homologous recombination DNA repair defects. Another validated, but as yet preclinical protein target, mandatory to BER is abasic (AP) endonuclease-1 (APE-1); in preclinical tests, APE-1 inhibition potentiates TMZ activity. An alternative strategy is synthesis of a molecule, evoking an irrepairable cytotoxic O6-G lesion. Preliminary efforts to achieve this goal are described.
581 citations
TL;DR: Mushrooms act as antibacterial, immune system enhancer and cholesterol lowering agents, and are important sources of bioactive compounds; additionally, some mushroom extracts are used to promote human health and are found as dietary supplements.
Abstract: Mushrooms have been consumed since earliest history; ancient Greeks believed that mushrooms provided strength for warriors in battle, and the Romans perceived them as the “Food of the Gods.” For centuries, the Chinese culture has treasured mushrooms as a health food, an “elixir of life.” They have been part of the human culture for thousands of years and have considerable interest in the most important civilizations in history because of their sensory characteristics; they have been recognized for their attractive culinary attributes. Nowadays, mushrooms are popular valuable foods because they are low in calories, carbohydrates, fat, and sodium: also, they are cholesterol-free. Besides, mushrooms provide important nutrients, including selenium, potassium, riboflavin, niacin, vitamin D, proteins, and fiber. All together with a long history as food source, mushrooms are important for their healing capacities and properties in traditional medicine. It has reported beneficial effects for health and treatment of some diseases. Many nutraceutical properties are described in mushrooms, such as prevention or treatment of Parkinson, Alzheimer, hypertension, and high risk of stroke. They are also utilized to reduce the likelihood of cancer invasion and metastasis due to antitumoral attributes. Mushrooms act as antibacterial, immune system enhancer and cholesterol lowering agents; additionally, they are important sources of bioactive compounds. As a result of these properties, some mushroom extracts are used to promote human health and are found as dietary supplements.
545 citations
"ENHANCED p53-DEPENDENT GROWTH INHIB..." refers background in this paper
...As mushrooms are one of the richest diversified sources of bioactive carbohydrates possess immunomodulatory, free radical scavenging, anti-tumour and anti-cancer activities [16-21, 31, 32]....
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