scholarly journals Enhanced Tumor Inhibitory Effects by Combining Metformin with Rosiglitazone in Glioblastoma Cells

2017 ◽  
Vol 99 (2) ◽  
pp. S188-S189
Author(s):  
C. Zhang
2015 ◽  
Vol 230 (8) ◽  
pp. 1713-1728 ◽  
Author(s):  
Yi Hu ◽  
Xing Lin ◽  
Ping Wang ◽  
Yi-Xue Xue ◽  
Zhen Li ◽  
...  

1995 ◽  
Vol 40 (4) ◽  
pp. 228-234 ◽  
Author(s):  
Koichi Iwasaki ◽  
Steven A. Toms ◽  
Gene H. Barnett ◽  
Melinda L. Estes ◽  
Manjula K. Gupta ◽  
...  

Author(s):  
Dongoh Kwak ◽  
Lars G J Hammarström ◽  
Martin Haraldsson ◽  
Patrik Ernfors

Abstract Background Increased membrane trafficking is observed in numerous cancer types, including glioblastoma. Targeting the oncogenic driven acquired alterations in membrane trafficking by synthetic cationic amphiphilic small molecules has recently been shown to induce death of glioblastoma cells, although the molecular targets are unknown. Methods The mechanism of action of the cationic amphiphilic drug Vacquinol-1 (Vacq1)-induced cytotoxicity was investigated using cell biology, biochemistry, functional experiments, chemical biology, unbiased antibody-based post-translation modification profiling and mass spectrometry-based chemical proteomic analysis on patient-derived glioblastoma cells. Results Vacq1 induced two types of abnormal endolysosomal vesicles, enlarged vacuoles and acidic vesicle organelles (AVOs). Mechanistically, enlarged vacuoles were formed by the impairment of lysosome reformation through the direct interaction and inhibition of calmodulin (CaM) by Vacq1, while AVO formation was induced by Vacq1 accumulation and acidification in the endosomal compartments through its activation of the v-ATPase. As a consequence of v-ATPase activation, cellular ATP consumption markedly increased, causing cellular energy shortage and cytotoxicity. This effect of Vacq1 was exacerbated by its inhibitory effects on calmodulin, causing lysosomal depletion and a failure of acidic vesicle organelle clearance. Conclusion Our study identifies the targets of Vacq1 and the mechanisms underlying its selective cytotoxicity in glioblastoma cells. The dual function of Vacq1 sets in motion a glioblastoma-specific vicious cycle of ATP consumption resulting in cellular energy crisis and cell death.


1995 ◽  
Vol 40 (4) ◽  
pp. 228-234 ◽  
Author(s):  
K. Iwasaki ◽  
Steven A. Toms ◽  
Gene H. Barnett ◽  
Melinda L. Estes ◽  
Manjula K. Gupta ◽  
...  

Author(s):  
Pınar Ercan ◽  
Sedef Nehir El

Abstract. The goals of this study were to determine and evaluate the bioaccessibility of total anthocyanin and procyanidin in apple (Amasya, Malus communis), red grape (Papazkarası, Vitis vinifera) and cinnamon (Cassia, Cinnamomum) using an in vitro static digestion system based on human gastrointestinal physiologically relevant conditions. Also, in vitro inhibitory effects of these foods on lipid (lipase) and carbohydrate digestive enzymes (α-amylase and α-glucosidase) were performed with before and after digested samples using acarbose and methylumbelliferyl oleate (4MUO) as the positive control. While the highest total anthocyanin content was found in red grape (164 ± 2.51 mg/100 g), the highest procyanidin content was found in cinnamon (6432 ± 177.31 mg/100 g) (p < 0.05). The anthocyanin bioaccessibilities were found as 10.2 ± 1%, 8.23 ± 0.64%, and 8.73 ± 0.70% in apple, red grape, and cinnamon, respectively. The procyanidin bioaccessibilities of apple, red grape, and cinnamon were found as 17.57 ± 0.71%, 14.08 ± 0.74% and 18.75 ± 1.49%, respectively. The analyzed apple, red grape and cinnamon showed the inhibitory activity against α-glucosidase (IC50 544 ± 21.94, 445 ± 15.67, 1592 ± 17.58 μg/mL, respectively), α-amylase (IC50 38.4 ± 7.26, 56.1 ± 3.60, 3.54 ± 0.86 μg/mL, respectively), and lipase (IC50 52.7 ± 2.05, 581 ± 54.14, 49.6 ± 2.72 μg/mL), respectively. According to our results apple, red grape and cinnamon have potential to inhibit of lipase, α-amylase and α-glucosidase digestive enzymes.


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