Statins: A Conceivable Remedial Role for the Regulation of Cancer Progression

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 angiogenesis. The induction of autophagy is another feature of statin effects that could contribute to the suppression of metastasis. Herein highlighted are the major signalling systems that statins engage to generate these biological effects. Statins can constrain tumour growth by influencing the expression and function of growth factor and receptor systems. They may suppress epithelial mesenchymal transition with resultant inhibition of cell survival signalling, together with the inhibition of cancer stem cell generation, and their maintenance and expansion. They can suppress ER (oestrogen receptor)-α in breast cancer cells. Statins have been implicated in the activation of the serine/threonine protein kinase AMPK (5' adenosine monophosphate-activated protein) leading to the suppression of cell proliferation. Both statins and bisphosphonates can supp...
Source: Current Cancer Therapy Reviews - Category: Cancer & Oncology Source Type: research

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Conclusions and Perspectives In this review, we have discussed important milestones from the early description of “Serum-sickness” as being due to antibodies directed against Neu5Gc epitopes all the way to the present-day therapeutic implications of these antibodies in cancer therapy. Some of these milestones have been represented in a concise timeline (Figure 6). While the “Xenosialitis” hypothesis is well-supported in the human-like mouse models, it has yet to be conclusively proven in humans. It remains to be seen if “Xenosialitis” plays a role in other uniquely-human diseases. FI...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
6-Bromoindirubin-3′-Oxime (6BIO) Suppresses the mTOR Pathway, Promotes Autophagy, and Exerts Anti-aging Effects in Rodent Liver Donghao Guo1, Yun Shen1, Wei Li1, Qinjie Li1, Yu Zhao2, Chenhao Pan3, Bi Chen3, Yuan Zhong1* and Ya Miao1* 1Department of Geriatrics, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China 2Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China 3Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China Liver aging is associated with a...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In conclusion, osmotic burst of inflated complement-damaged cells may occur, but these bursts are most likely a consequence of metabolic collapse of the cell rather than the cause of cell death. The Complement Cell Death Mediator: A Concerted Action of Toxic Moieties Membrane pores caused by complement were first visualized by electron microscopy on red blood cell membranes as large ring structures (22). Similar lesions were viewed on E. coli cell walls (23). Over the years, ample information on the fine ultrastructure of the MAC that can activate cell death has been gathered (24) and has been recently further examined (...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Publication date: Available online 5 April 2019Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): Faegheh Ghanbari, Andrea Hebert-Losier, Janelle Barry, Donald Poirier, Vincent Giguere, Sylvie Mader, Anie PhilipAbstractEstrogen-receptor related receptors (ERRs) which consists of ERRα, ERRβ and ERRγ belong to the orphan nuclear receptor subfamily 3, group B (NR3B) subfamily, and are constitutively active. ERRs have been shown to actively modulate estrogenic responses, and to play an essential role in pregnancy, and are implicated in breast cancer progression. Despite intensive effor...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research
Abstract The changes in cellular metabolism play an important role in promoting tumor progression. Recent findings suggested that the mutation of tumor suppressor gene p53 promoted lipids synthesis and mutant p53 (mutp53) was essential for regulating mevalonate pathway for cholesterol synthesis. Simvastatin, a 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor, was found to exhibit therapeutic effects against many types of cancers including breast cancer, colon cancer, lung cancer, etc. However, the underlying mechanism of the antitumor effect of simvastatin still needs to be further investigated...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research
Abstract Dysregulation of steroid biosynthesis has been implicated in the pathophysiology of a variety of cancers. One such common malignancy in women is breast cancer that is frequently promoted by estrogen overproduction. All steroid hormones are made from cholesterol, and the rate-limiting step in steroid biosynthesis is primarily mediated by the steroidogenic acute regulatory (StAR) protein. Whereas the involvement of StAR in the regulation steroid hormone biosynthesis is well established, its association to breast cancer remains obscure. Herein, we report that estrogen receptor positive breast cancer cell lin...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research
This study's researchers approached all people turning 85 in 2006 in two cities in the UK for participation. At the beginning of the study in 2006-2007, there were 722 participants, 60 percent of whom were women. The participants provided researchers with information about what they ate every day, their body weight and height measurements, their overall health assessment (including any level of disability), and their medical records. The researchers learned that more than one-quarter (28 percent) of very old adults had protein intakes below the recommended dietary allowance. The researchers noted that older adults w...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Journal of Cellular Biochemistry, EarlyView.
Source: Journal of Cellular Biochemistry - Category: Biochemistry Authors: Source Type: research
Abstract To assess differences in the receipt of preventive health services by race/ethnicity among older women with endometrial cancer enrolled in Medicare, we conducted a retrospective population‐based cohort study of women diagnosed with endometrial cancer from 2001 to 2011 in the Surveillance Epidemiology and End Results (SEER)‐Medicare database. Women with stage I or II endometrial cancer of epithelial origin were included. The exposure was race/ethnicity (Non‐Hispanic [NH] White, NH Black, Hispanic, and NH Asian/Pacific Islander [PI]). The services examined were receipt of influenza vaccination and screening te...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: Original Research Source Type: research
Abstract Several studies have suggested an etiological role for hypercholesterolemia in the pathogenesis of breast cancer and prostate cancer (PCa). However, the molecular mechanisms that underlie and mediate the hypercholesterolemia-fostered increased risk for breast cancer and PCa are yet to be determined. The discovery that the most abundant cholesterol oxidized metabolite in the plasma, 27 hydroxycholesterol (27-OHC), is a selective estrogen receptor modulator (SERM) and an agonist of Liver X receptors (LXR) partially fills the void in our understanding and knowledge of the mechanisms that may link hypercholes...
Source: Medical Physics - Category: Physics Authors: Tags: Chem Phys Lipids Source Type: research
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