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Cholesterol homeostasis and functions. Cholesterol homeostasis is tightly regulated in our body and can be achieved through intricate mechanisms involved in biosynthesis, dietary absorption, transportation (influx or efflux), catabolism, and depletion. The functions of cholesterol are composed of distinct membrane, control membrane fluidity and protein recruitment, produce steroid and oxysterol, and are involved in cell signaling to regulate cell growth, proliferation , and migration.
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The accumulation of cholesterol in cancer cells and tumor tissues promotes cell growth, proliferation, and migration as well as tumor progression. Cholesterol synthesis is catalyzed by a series of enzymatic reactions. Regulation of these key enzymes can control cholesterol synthesis and modulate cellular cholesterol levels in the cells. Meanwhile,...
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... cholesterol is a risk factor to numerous pathologies such as cardiovascular disease, atherosclerosis, dyslipidemia, and neurodegenerative diseases and is associated with the development of diabetes and cancer. Cholesterol homeostasis is achieved through intricate mechanisms involving biosynthesis, catabolism, dietary absorption, trans- portation (influx or efflux), and depletion (Figure 2) [28][29][30][31][32]. Slightly less than half of cholesterol in our body derives from de novo biosynthesis every day. The liver is the dominant site of cholesterol biosynthesis, and in vivo liver cholesterol production has been estimated at 1-2 g/ day. ...
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... to cholesterol homeostasis leads to a variety of diseases such as coronary heart disease, atherosclerosis, and metabolic syndrome as well as cancer [9][10][11][12][13][14][15][16][17][18][19][45][46][47][48][49][50][51]. This indicates that cholesterol plays a crucial role in the regulation of cellular function (Figure 2). In the cells, cholesterol is mandatory for cellular growth and serves as one of the necessary building blocks for new membranes demanded by dividing cells during proliferation. ...
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... Alkaloids are reported to have analgesic, anti-inflammatory function and help to alleviate pain, develop resistance against diseases and endurance against stress [18] . Studies have shown that saponins found in plants have anti-tumour and anti-mutagenic properties and can also lower the risk of cancer cells [19] . They reduce the growth and viability of the cancer cells by reacting with cholesterol rich membranes of these cancer cells [19,20] . ...
... Studies have shown that saponins found in plants have anti-tumour and anti-mutagenic properties and can also lower the risk of cancer cells [19] . They reduce the growth and viability of the cancer cells by reacting with cholesterol rich membranes of these cancer cells [19,20] . Plants or extracts of plants containing cardiac glycosides have been used as emetics, diuretics and heart tonics. ...
In spite of the richness in nutritive values, minerals and vitamins content of chlorophyll which is highly contained in carrot greens, these greens are usually cut and thrown away as waste, these underutilizations of the carrot greens instigated the investigation for biological compounds of medicinal importance. This research is focus on the investigation of tannins in carrots greens and its biological activity, via extraction in 70 % acetone and partitioning in diethyl ether and distilled water. The extract was subjected to phytochemical screening, thin layer chromatography (TLC), column chromatography (CC) and antimicrobial activity test. The isolation of the tannins was carried out by preparative thin layer chromatography (PrepTLC). The isolated tannin was further analysed by TLC using ethylacetate-ethanol-water (8:2:1.5) as solvent system along with standard tannins, high performance liquid chromatography (HPLC) and fourier tranform infra-red spectroscopy. The plant extract gave a percentage extract of 5.45, 2.24 of aqueous and 3.22 of diethyl ether fractions after partitioning. The phytochemical screening of the crude gave tannins, alkaloids, flavonoids, saponins, cardiac glycosides and phenols. The TLC result of the isolated tannin revealed three (3) different tannins out of which two (2) matched with standard gallic acid and catechol according to similarity in Rf values (0.47 and 0.76 respectively). The HPLC analysis of the tannin also confirmed the appearance of three different tannins peaks eluting at retention times 2.199, 2.967 and 4.944 mins. The FT-IR supports the presence of the suspected compounds by showing broad absorptions peaks at 3348cm-1 for OH stretch, a medium peak at 1643cm-1 resulting from C=C aromatic stretch, and CO absorption at 1211cm-1. Both crude and aqueous fraction of the extract show positive activity on some gram-positive organism. The activity on Streptococcus pneumoniae of the tannin fraction is concentration dependant and these indicated that it can be used as remedy in respiratory tract infections such as those caused or aggrevated by S. pneumoniae. The appreciable quantity of flavonoids and tannins indicates they can be responsible for healings of wounds, inflamed mucous membranes, venous ulcers and exhibit radical scavenging activities.
... CpG treatment elicited a variety of immune responses, with the 3 most significantly enriched GO terms of 1) proteolysis, 2) negative regulation of inflammatory response, and 3) immune system process. Unique GO terms include the positive regulation of release of sequestered calcium ion into cytosol, which may trigger autophagy in cancer (Danese et al., 2017;Kania et al., 2017); negative regulation of cholesterol storage and positive regulation of cholesterol transport, which has been associated with inhibiting tumor growth and progression (Huang and Freter, 2016); chemotaxis, and Thelper 17 cell lineage commitment, where T-helper 17 cells may have both anti-tumor and pro-tumoral properties (Dahal, 2017); and KEGG term of PPAR signaling pathway, where PPARs have implications in both promoting and preventing cancer (Youssef and Badr, 2011). ...
Cancer immunotherapy aims to stimulate immune cells to recognize and attack tumor tissue. The immunostimulatory polyanions polyI:C and CpG induce potent pro-inflammatory immune responses as TLR3 and TLR9 agonists, respectively. Clinical trials of TLR agonists, however, have been fraught with immune-related adverse events, even when injecting intratumorally in an effort to minimize systemic exposure. We identified Glatiramer Acetate (GA), a positively-charged polypeptide approved for multiple sclerosis, as a delivery agent capable of complexing with polyI:C or CpG and reducing the mobility of these actives. Small nanoparticles termed polyplexes form when mixing positively-charged GA and negatively-charged immunostimulant (polyI:C or CpG). The ratio of GA to immunostimulant directly affected the potency of TLR activation and the mobility of these actives in simulated tumor tissue. Polyplexes of GA and CpG were injected intratumorally in a tumor model of head and neck squamous cell carcinoma (HNSCC) and significantly mitigated tumor growth as compared to the vehicle controls. Intratumoral injections of CpG showed the slowest tumor growth but exhibited dramatically higher systemic proinflammatory cytokine levels compared to polyplexes of GA with CpG. Sequencing of resected tumors revealed a similar pattern of upregulated proinflammatory cytokines for CpG and polyplexes, a finding supported by histological tumor staining showing similar infiltration of immune cells induced by these treatments. Intratumoral administration of polyplexes of GA with immunostimulant represents a translational approach to enhance local immune responses while mitigating systemic immune-related adverse events.
Peptide therapy has started since 1920s with the advent of insulin application, and now it has emerged as a new approach in treatment of diseases including cancer. Using anti-cancer peptides (ACPs) is a promising way of cancer therapy as ACPs are continuing to be approved and arrived at major pharmaceutical markets. Traditional cancer treatments face different problems like intensive adverse effects to patient's body, cell resistance to conventional chemical drugs and in some worse cases the occurrence of cell multidrug resistance (MDR) of cancerous tissues against chemotherapy. On the other hand, there are some benefits conceived for peptides usage in treatment of diseases specifically cancer, as these compounds present favorable characteristics such as smaller size, high activity, low immunogenicity, good biocompatibility in vivo, convenient and rapid way of synthesis, amenable to sequence modification and revision and there is no limitation for the type of cargo they carry. It is possible to achieve an optimum molecular and functional structure of peptides based on previous experience and bank of peptide motif data which may result in novel peptide design. Bioactive peptides are able to form pores in cell membrane and induce necrosis or apoptosis of abnormal cells. Moreover, recent researches have focused on the tumor recognizing peptide motifs with the ability to permeate to cancerous cells with the aim of cancer treatment at earlier stages. In this strategy the most important factors for addressing cancer are choosing peptides with easy accessibility to tumor cell without cytotoxicity effect towards normal cells. The peptides must also meet acceptable pharmacokinetic requirements. In this review, the characteristics of peptides and cancer cells are discussed. The various mechanisms of peptides' action proposed against cancer cells make the next part of discussion. It will be followed by giving information on peptides application, various methods of peptide designing along with introducing various databases. Future aspects of peptides for employing in area of cancer treatment come as conclusion at the end.
Alteration of lipid metabolism plays a critical role in the development of many types of cancer including breast cancer. Lipid metabolism can be regulated by a variety of signaling pathways with proliferative stimuli, apoptotic stimuli or environment changes under physiological, pathophysiological or therapeutic conditions. On the other hand, many lipids and lipid intermediate metabolites are also important signaling molecules involved in cell signaling that regulate cell proliferation, differentiation, apoptosis and migration as well as responses to drug treatment. In physiological condition, lipid metabolism (anabolism and catabolism) is tightly regulated by signaling network in the cell under designed path to growth, proliferation, differentiation and migration. Dysregulation of lipid metabolism under pathological condition leads to alteration of lipid profiles and accumulation of some “bad” lipids which can cause cell overgrowth and hyper-proliferation such as cancer and cell death such as tissue injury (Fig. 8.3). This chapter focuses on the emerging understanding of the role of lipid metabolic pathway in breast carcinogenesis and tumor progression. The update information indicates that the modulation of lipid metabolism can potentially be exploited to prevent breast cancer and enhance efficacy of breast cancer therapy.
