[show abstract][hide abstract] ABSTRACT: Cancer cachexia is a debilitating consequence of disease progression, characterised by the significant weight loss through the catabolism of both skeletal muscle and adipose tissue, leading to a reduced mobility and muscle function, fatigue, impaired quality of life and ultimately death occurring with 25-30 % total body weight loss. Degradation of proteins and decreased protein synthesis contributes to catabolism of skeletal muscle, while the loss of adipose tissue results mainly from enhanced lipolysis. These mechanisms appear to be at least, in part, mediated by systemic inflammation. Exercise, by virtue of its anti-inflammatory effect, is shown to be effective at counteracting the muscle catabolism by increasing protein synthesis and reducing protein degradation, thus successfully improving muscle strength, physical function and quality of life in patients with non-cancer-related cachexia. Therefore, by implementing appropriate exercise interventions upon diagnosis and at various stages of treatment, it may be possible to reverse protein degradation, while increasing protein synthesis and lean body mass, thus counteracting the wasting seen in cachexia.
Journal of cachexia, sarcopenia and muscle. 12/2012;
[show abstract][hide abstract] ABSTRACT: Plants have proved to be an important source of anti-cancer drugs. Here we have investigated the cytotoxic action of an aqueous extract of Fagonia cretica, used widely as a herbal tea-based treatment for breast cancer.
Using flow cytometric analysis of cells labeled with cyclin A, annexin V and propidium iodide, we describe a time and dose-dependent arrest of the cell cycle in G0/G1 phase of the cell cycle and apoptosis following extract treatment in MCF-7 (WT-p53) and MDA-MB-231 (mutant-p53) human breast cancer cell lines with a markedly reduced effect on primary human mammary epithelial cells. Analysis of p53 protein expression and of its downstream transcription targets, p21 and BAX, revealed a p53 associated growth arrest within 5 hours of extract treatment and apoptosis within 24 hours. DNA double strand breaks measured as γ-H2AX were detected early in both MCF-7 and MDA-MB-231 cells. However, loss of cell viability was only partly due to a p53-driven response; as MDA-MB-231 and p53-knockdown MCF-7 cells both underwent cell cycle arrest and death following extract treatment. p53-independent growth arrest and cytotoxicity following DNA damage has been previously ascribed to FOXO3a expression. Here, in MCF-7 and MDA-MB-231 cells, FOXO3a expression was increased significantly within 3 hours of extract treatment and FOXO3 siRNA reduced the extract-induced loss of cell viability in both cell lines.
Our results demonstrate for the first time that an aqueous extract of Fagonia cretica can induce cell cycle arrest and apoptosis via p53-dependent and independent mechanisms, with activation of the DNA damage response. We also show that FOXO3a is required for activity in the absence of p53. Our findings indicate that Fagonia cretica aqueous extract contains potential anti-cancer agents acting either singly or in combination against breast cancer cell proliferation via DNA damage-induced FOXO3a and p53 expression.
PLoS ONE 01/2012; 7(6):e40152. · 3.73 Impact Factor