p53 in Human Cancer — Somatic and Inherited Mutations and Mutation-independent Mechanisms

Author(s):  
Ute M. Moll ◽  
Nicole Concin
2018 ◽  
Vol 98 (2) ◽  
pp. 559-621 ◽  
Author(s):  
Natalia Prevarskaya ◽  
Roman Skryma ◽  
Yaroslav Shuba

Genomic instability is a primary cause and fundamental feature of human cancer. However, all cancer cell genotypes generally translate into several common pathophysiological features, often referred to as cancer hallmarks. Although nowadays the catalog of cancer hallmarks is quite broad, the most common and obvious of them are 1) uncontrolled proliferation, 2) resistance to programmed cell death (apoptosis), 3) tissue invasion and metastasis, and 4) sustained angiogenesis. Among the genes affected by cancer, those encoding ion channels are present. Membrane proteins responsible for signaling within cell and among cells, for coupling of extracellular events with intracellular responses, and for maintaining intracellular ionic homeostasis ion channels contribute to various extents to pathophysiological features of each cancer hallmark. Moreover, tight association of these hallmarks with ion channel dysfunction gives a good reason to classify them as special type of channelopathies, namely oncochannelopathies. Although the relation of cancer hallmarks to ion channel dysfunction differs from classical definition of channelopathies, as disease states causally linked with inherited mutations of ion channel genes that alter channel's biophysical properties, in a broader context of the disease state, to which pathogenesis ion channels essentially contribute, such classification seems absolutely appropriate. In this review the authors provide arguments to substantiate such point of view.


2019 ◽  
Vol 476 (24) ◽  
pp. 3687-3704 ◽  
Author(s):  
Aphrodite T. Choumessi ◽  
Manuel Johanns ◽  
Claire Beaufay ◽  
Marie-France Herent ◽  
Vincent Stroobant ◽  
...  

Root extracts of a Cameroon medicinal plant, Dorstenia psilurus, were purified by screening for AMP-activated protein kinase (AMPK) activation in incubated mouse embryo fibroblasts (MEFs). Two isoprenylated flavones that activated AMPK were isolated. Compound 1 was identified as artelasticin by high-resolution electrospray ionization mass spectrometry and 2D-NMR while its structural isomer, compound 2, was isolated for the first time and differed only by the position of one double bond on one isoprenyl substituent. Treatment of MEFs with purified compound 1 or compound 2 led to rapid and robust AMPK activation at low micromolar concentrations and increased the intracellular AMP:ATP ratio. In oxygen consumption experiments on isolated rat liver mitochondria, compound 1 and compound 2 inhibited complex II of the electron transport chain and in freeze–thawed mitochondria succinate dehydrogenase was inhibited. In incubated rat skeletal muscles, both compounds activated AMPK and stimulated glucose uptake. Moreover, these effects were lost in muscles pre-incubated with AMPK inhibitor SBI-0206965, suggesting AMPK dependency. Incubation of mouse hepatocytes with compound 1 or compound 2 led to AMPK activation, but glucose production was decreased in hepatocytes from both wild-type and AMPKβ1−/− mice, suggesting that this effect was not AMPK-dependent. However, when administered intraperitoneally to high-fat diet-induced insulin-resistant mice, compound 1 and compound 2 had blood glucose-lowering effects. In addition, compound 1 and compound 2 reduced the viability of several human cancer cells in culture. The flavonoids we have identified could be a starting point for the development of new drugs to treat type 2 diabetes.


Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
S Nam ◽  
R Buettner ◽  
X Liu ◽  
J Turkson ◽  
D Kim ◽  
...  

Planta Medica ◽  
2007 ◽  
Vol 73 (09) ◽  
Author(s):  
IO Mondranondra ◽  
A Suedee ◽  
A Kijjoa ◽  
M Pinto ◽  
N Nazareth ◽  
...  

10.33540/153 ◽  
2020 ◽  
Author(s):  
◽  
Krijn Kristian Dijkstra
Keyword(s):  

2012 ◽  
Vol 17 (2) ◽  
pp. 123-143 ◽  
Author(s):  
Christina Schonherr ◽  
Bengt Hallberg ◽  
Ruth Palmer

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