Lovastatin-mediated MCF-7 cancer cell death involves LKB1-AMPK-p38MAPK-p53-survivin signalling cascade.

In this study, we explored the anti-tumour mechanisms of a lipophilic statin, lovastatin, in MCF-7 breast cancer cells. Lovastatin inhibited cell proliferation and induced cell apoptosis. Lovastatin caused p21 elevation while reduced cyclin D1 and survivin levels. Lovastatin also increased p53 phosphorylation, acetylation and its reporter activities. Results from chromatin immunoprecipitation analysis showed that p53 binding to the survivin promoter region was increased, while Sp1 binding to the region was decreased, in MCF-7 cells after lovastatin exposure. These actions were associated with liver kinase B1 (LKB1), AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (p38MAPK) activation. Lovastatin's enhancing effects on p53 activation, p21 elevation and survivin reduction were significantly reduced in the presence of p38MAPK signalling inhibitor. Furthermore, LKB1-AMPK signalling blockade abrogated lovastatin-induced p38MAPK and p53 phosphorylation. Together these results suggest that lovastatin may activate LKB1-AMPK-p38MAPK-p53-survivin cascade to cause MCF-7 cell death. The present study establishes, at least in part, the signalling cascade by which lovastatin induces breast cancer cell death. PMID: 31821701 [PubMed - as supplied by publisher]
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research

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In conclusion, it remains unclear if brain-specific regional and temporal changes occur in the expression of the different APP variants during AD progression. Since APP is also found in blood cells, assessing the changes in APP mRNA expression in peripheral blood cells from AD patients has been considering an alternative. However, again the quantification of APP mRNA in peripheral blood cells has generated controversial results. Brain APP protein has been analyzed in only a few studies, probably as it is difficult to interpret the complex pattern of APP variants and fragments. We previously characterized the soluabl...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Authors: Alarfi H, Youssef LA, Salamoon M Abstract Preclinical studies support the anticancer activity of statins; however, the existing clinical evidence is inconsistent and not definitive. Our study aimed at evaluating a postulated cancer chemo-sensitizing effect of statin (simvastatin) in a cohort of metastatic breast cancer (MBC) patients. We designed a prospective, single-centered, randomized, double blinded, placebo-controlled trial that encompassed MBC patients with an ECOG Performance Status Scale ≤2 and scheduled to be treated with a chemotherapy regimen consisting of carboplatin and vinorelbine every 3...
Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research
In this study, we sought to elucidate the role of VRK-1 in regulation of adult life span in C. elegans. We found that overexpression of VRK-1::GFP (green fluorescent protein), which was detected in the nuclei of cells in multiple somatic tissues, including the intestine, increased life span. Conversely, genetic inhibition of vrk-1 decreased life span. We further showed that vrk-1 was essential for the increased life span of mitochondrial respiratory mutants. We demonstrated that VRK-1 was responsible for increasing the level of active and phosphorylated form of AMPK, thus promoting longevity. A Fisetin Variant, C...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Chemotherapy has led to improved survival in patients with breast cancer; however, it is associated with an increased risk of cardiac dysfunction and heart failure. We investigated the protective effects of rosuvastatin and candesartan, alone and in combination, in a doxorubicin- and trastuzumab-induced rat model of cardiomyopathy.
Source: Journal of the American Society of Echocardiography - Category: Cardiology Authors: Source Type: research
AbstractPurpose of ReviewPatients with cancer have an elevated risk of cardiovascular disease. This review describes the cardiovascular risks of different cancer therapies and the evidence for cardioprotective strategies.Recent FindingsRecent studies have provided additional support for the safety and efficacy of dexrazoxane and liposomal anthracycline formulations in certain high-risk patients receiving anthracyclines and for neurohormonal antagonist therapy in patients with breast cancer receiving sequential anthracyclines and trastuzumab. Ongoing studies are exploring the benefit of: (1) statins for anthracycline cardio...
Source: Current Oncology Reports - Category: Cancer & Oncology Source Type: research
Conclusions: We did not find any association between ADM use and disease-specific mortality among women with T2D diagnosed with breast cancer. However, interestingly, prediagnostic statin use was observed to predict reduced mortality from breast cancer and other causes. We hypothesise that treating treatment practices of T2D or hypercholesterolaemia of breast cancer patients might affect overall prognosis of women diagnosed with breast cancer and T2D. PMID: 32478629 [PubMed - as supplied by publisher]
Source: Acta Oncologica - Category: Cancer & Oncology Authors: Tags: Acta Oncol Source Type: research
This article summarizes the clinical questions and bottom-line answers from the top 20 POEMs of 2019. Taking blood pressure medications at night results in a large mortality reduction over six years compared with morning dosing. Automated devices are the best way to measure blood pressure. Nonfasting lipid profiles are preferred over fasting lipid profiles, and nonfasting and fasting lipid profiles are equally effective at predicting risk. The benefit of statins for primary prevention in people 75 years and older is uncertain at best. Aspirin has no net benefit for primary prevention of cardiovascular disease and has no ef...
Source: American Family Physician - Category: Primary Care Authors: Tags: Am Fam Physician Source Type: research
Abstract PURPOSE: In this prospective longitudinal study, Coronary Artery Calcium (CAC) scores determined before the start of whole breast irradiation were compared with those determined 7 years afterwards. The aim was to examine whether the use of a breath-hold (BH) technique is associated with less increase of CAC scores. METHODS AND MATERIALS: Changes in CAC scores were analysed in 87 breast cancer patients. The results of the following groups were compared: patients receiving right (R) or left-sided radiotherapy using free breathing (L-FB) with those receiving left-sided radiotherapy with BH (L-BH). We co...
Source: Radiotherapy and Oncology : journal of the European Society for Therapeutic Radiology and Oncology - Category: Radiology Authors: Tags: Radiother Oncol Source Type: research
This article summarizes the clinical questions and bottom-line answers from the top 20 POEMs of 2019. Taking blood pressure medications at night results in a large mortality reduction over six years compared with morning dosing. Automated devices are the best way to measure blood pressure. Nonfasting lipid profiles are preferred over fasting lipid profiles, and nonfasting and fasting lipid profiles are equally effective at predicting risk. The benefit of statins for primary prevention in people 75 years and older is uncertain at best. Aspirin has no net benefit for primary prevention of cardiovascular disease and has no ef...
Source: Pain Physician - Category: Anesthesiology Authors: Tags: Am Fam Physician Source Type: research
Conclusion: Our study provides weak evidence to support the use of genetic variation in ABCB1, SLCO1B1, CYP3A4, and CYP3A5 as biomarkers of breast tumor response to simvastatin. Validation of these findings within adjuvant clinical trials is encouraged. PMID: 32351149 [PubMed - as supplied by publisher]
Source: Acta Oncologica - Category: Cancer & Oncology Authors: Tags: Acta Oncol Source Type: research
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