geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Increased betulinic acid induced cytotoxicity and radiosensitivity in glioma cells under hypoxic conditions


, : Increased betulinic acid induced cytotoxicity and radiosensitivity in glioma cells under hypoxic conditions. Radiation Oncology 6(): 111-111

Betulinic acid (BA) is a novel antineoplastic agent under evaluation for tumor therapy. Because of the selective cytotoxic effects of BA in tumor cells (including gliomas), the combination of this agent with conservative therapies (such as radiotherapy and chemotherapy) may be useful. Previously, the combination of BA with irradiation under hypoxic conditions had never been studied. In this study, the effects of 3 to 30 μM BA on cytotoxicity, migration, the protein expression of PARP, survivin and HIF-1α, as well as radiosensitivity under normoxic and hypoxic conditions were analyzed in the human malignant glioma cell lines U251MG and U343MG. Cytotoxicity and radiosensitivity were analyzed with clonogenic survival assays, migration was analyzed with Boyden chamber assays (or scratch assays) and protein expression was examined with Western blot analyses. Under normoxic conditions, a half maximal inhibitory concentration (IC50) of 23 μM was observed in U251MG cells and 24 μM was observed in U343MG cells. Under hypoxic conditions, 10 μM or 15 μM of BA showed a significantly increased cytotoxicity in U251MG cells (p = 0.004 and p = 0.01, respectively) and U343MG cells (p < 0.05 and p = 0.01, respectively). The combination of BA with radiotherapy resulted in an additive effect in the U343MG cell line under normoxic and hypoxic conditions. Weak radiation enhancement was observed in U251MG cell line after treatment with BA under normoxic conditions. Furthermore, under hypoxic conditions, the incubation with BA resulted in increased radiation enhancement. The enhancement factor, at an irradiation dose of 15 Gy after treatment with 10 or 15 μM BA, was 2.20 (p = 0.02) and 4.50 (p = 0.03), respectively. Incubation with BA led to decreased cell migration, cleavage of PARP and decreased expression levels of survivin in both cell lines. Additionally, BA treatment resulted in a reduction of HIF-1α protein under hypoxic conditions. Our results suggest that BA is capable of improving the effects of tumor therapy in human malignant glioma cells, particularly under hypoxic conditions. Further investigations are necessary to characterize its potential as a radiosensitizer.

US$19.90

PMID: 21906280

DOI: 10.1186/1748-717X-6-111


Other references

Rossovskiy L.N., 1990: Correlation of constant and eutectic crystallization and metasomatism during formation of rare metal granite pegmatites; example from Hindu Kush. Doklady Akademii Nauk Tadzhikskoy SSR 33(6): 404-407

Beever, J.E.; Lewin, H.A., 1992: RFLP at the bovine phosphogluconate dehydrogenase (PGD) locus. Using a 0.8-kb cDNA clone encoding human phosphogluconase dehydrogenase, a 2-allele restriction fragment length polymorphism was detected in cattle; the alleles segregated in an autosomal fashion in 61 half-sibs sired by a heterozygous bull.

Quinones, A.-Moreno; Torres, J.-Rentas; Rubin, M., R., 2006: Biochemical detection, pharmacological inhihition, and phylogenetic analysis of Caenorhabditis elegans metalloproteases. Metalloproteases comprise a diverse superfamily of proteases with a requirement for a metal ion in their catalytic site. These proteins have been shown to play a role in many biological processes including fertilization, cellular adhesion, develo...

Weilenmann, F.; Winzeler, H.; Fried, P.M.; Saurer, W., 1985: Spring cereal cultivation. For 7 varieties of spring wheat, 4 varieties of spring barley and 5 varieties of spring oats, information is presented on performance in yield trials during 1981-84, and on characters including earliness, lodging resistance and disease resistance....

Safer, D.; Elzinga, M., 1996: Thymosin b-4 crosslinks to the barbed end of the actin monomer. Biophysical Journal 70(2 PART 2): A125

L.C.angSheng; Zhang ZhiMing; M.L.Juan, 2001: Performance of Jinzhou-Black-Standard mink (JBS mink). JBS-mink, a new variety of mink, was obtained by crossing American mink with Danish mink. The resulting variety was found to have excellent performance. It is suitable for being raised in areas around the latitude of 35 degrees north. The overall...

Beuchat L.R.; Nakayama T.; Phillips R.D.; Worthington R.E., 1985: Comparison of soybeans glycine max peanuts arachis hypogaea and cowpeas vigna unguiculata as substrates for preparing natto. Six strains of Bacillus subtilis (B. natto) were tested for their ability to ferment soybeans in the preparation of natto. One strain was further tested using peanuts and cowpeas as substrates in addition to soybeans. Conditions of rehydration, st...

Wesslau, C.; Gmyrek, G., 1986: Correction of severe metabolic alkalosis with extrarenal-induced renal failure by treatment with hemodialysis. Anaesthesiologie und Reanimation 11(4): 235-240

Saifullah, S.; Steven, D., 1974: The phytoplankton of St. Margarets Bay. Botanica marina: 17 (2) 107-112

Kalab, M., 1966: Arginase isoenzymes. The heterogeneity of arginase in human erythrocytes was demonstrated using electrophoretic separation. The use of 1% agar gel in a veronal-acetate buffer of pH 8.6 allowed the demonstration of the existence of 6 zones of arginase activity. An inve...