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]
Survivin has an anti-apoptotic effect against anthracycline-induced cardiotoxicity. Clinically, statin use is associated with a lower risk for heart failure in breast cancer patients with anthracycline chemotherapy. So, the purpose of our study was to investigate whether survivin mediates the protective effect of statin against anthracycline-induced cardiotoxicity.
Conclusions: Many of the trials that have established the efficacy and safety of statins were conducted predominantly or entirely in men, with results extrapolated to women. Additional research is needed to guide clinical recommendations specific to women. Video Summary:http://links.lww.com/MENO/A462.
Results could cause patients undue worry or inappropriate reassurance – and increase workload for GP teams Related items fromOnMedica Doctors campaign against ‘too much medicine’ NHS must improve access to screening to save lives Metastatic breast cancer goes undiagnosed for too long Statins of small and uncertain benefit in primary prevention Pharmacists could offer high-dose statins direct to patients
(CNN) — Leading nutritional experts in the United States and the UK are fired up about new dietary recommendations claiming there’s no need to reduce your red and processed meat intake for good health. “This is a very irresponsible public health recommendation,” said Dr. Frank Hu, who chairs the nutrition department at the Harvard T.H. Chan School of Public Health. The new guidelines and five corresponding studies are part of a systematic analysis of existing research done by NutriRECS, a recently formed international group of nutritionists and health researchers. NutriRECS says its mission is to &l...
ConclusionsThese analyses suggest the pharmacokinetic profile of darolutamide is not affected by a number of commonly administered drugs in patients with nmCRPC. Although pharmacokinetic data have indicated that darolutamide has the potential to interact with rosuvastatin, used to assess DDI in these studies, this finding did not seem to translate into increased AEs due to statin use in the ARAMIS trial.Clinicaltrials.gov identifier: NCT02200614.
Conclusion: Future studies are needed to assess the effect of statins in risk reduction and to identify other drugs with chemopreventive potential against CBC. Eventually, efforts must be directed towards identifying those breast cancer patients likely to benefit most from specific preventive therapies. PMID: 31393200 [PubMed - as supplied by publisher]
The mevalonate pathway (also known as the cholesterol biosynthesis pathway) plays a crucial metabolic role in normal cell function as well as in the pathological environment. It leads to the synthesis of sterol and non-sterol isoprenoid biomolecules which subserve a variety of cellular functions. It is known to be deregulated in many disease processes. Statins and bisphosphonates are prominent inhibitors of the mevalonate pathway. They inhibit cell proliferation and activate apoptotic signalling and suppress tumour growth. Statins subdue metastatic spread of tumours by virtue of their ability to suppress invasion and angio...
Publication date: 25 June 2019Source: Cell Reports, Volume 27, Issue 13Author(s): Sidse Ehmsen, Martin H. Pedersen, Guisong Wang, Mikkel G. Terp, Amina Arslanagic, Brian L. Hood, Thomas P. Conrads, Rikke Leth-Larsen, Henrik J. DitzelSummaryTumor eradication may be greatly improved by targeting cancer stem cells (CSCs), as they exhibit resistance to conventional therapy. To gain insight into the unique biology of CSCs, we developed patient-derived xenograft tumors (PDXs) from ER− breast cancers from which we isolated mammospheres that are enriched for CSCs. Comparative global proteomic analysis was performed on patien...
Condition: Breast Cancer Female Interventions: Drug: statins; Behavioral: Dietary intervention group (control group) Sponsor: Peking Union Medical College Hospital Recruiting
Authors: Talaiezadeh A, Papan AM, Nazari P, Mousavi Ghanavati SP, Ramazani A PMID: 31127876 [PubMed - in process]