stearates and Neoplasms

We have explored the causes of the major chronic diseases prevailing in the world and the relevant mechanisms as a sound basis for recommendations for their prevention. Research shows that the cocoa bean, and tasty products derived from the cocoa bean such as chocolate, and the beverage cocoa, popular with many people worldwide, is rich in specific antioxidants, with the basic structure of catechins and epicatechin, and especially the polymers procyanidins, polyphenols similar to those found in vegetables and tea. Metabolic epidemiological studies indicate that regular intake of such products increases the plasma level of antioxidants, a desirable attribute as a defense against reactive oxygen species (ROS). The antioxidants in cocoa can prevent the oxidation of LDL-cholesterol, related to the mechanism of protection in heart disease. Likewise, a few studies show that ROS associated with the carcinogenic processes is also inhibited, although there have not been many studies on a possible lower risk of various types of cancer either in humans or in animal models consuming cocoa butter or chocolates. Based on the knowledge acquired thus far, it would seem reasonable to suggest inhibition of the several phases of the complex processes leading to cancer, as a function of quantitative intake of antioxidants, including those from cocoa and chocolates. Cocoa and chocolate also contain fats from cocoa butter. These are mainly stearic triglycerides (C18:0) that are less well absorbed than other fats, and are excreted in the feces. Thus, cocoa butter is less bioavailable and has minimal effect on serum cholesterol.

Topics: Antioxidants; Cacao; Cholesterol, LDL; Chronic Disease; Coronary Disease; Flavonoids; Humans; Lipid Metabolism; Lipids; Neoplasms; Phenols; Polymers; Polyphenols; Reactive Oxygen Species; Stearates

Reprogramming of lipid metabolism is emerging as a hallmark of cancer, yet involvement of specific fatty acids (FA) species and related enzymes in tumorigenesis remains unclear. While previous studies have focused on involvement of long-chain fatty acids (LCFAs) including palmitate in cancer, little attention has been paid to the role of very long-chain fatty acids (VLCFAs). Here, we show that depletion of acetyl-CoA carboxylase (ACC1), a critical enzyme involved in the biosynthesis of fatty acids, inhibits both de novo synthesis and elongation of VLCFAs in human cancer cells. ACC1 depletion markedly reduces cellular VLCFA but only marginally influences LCFA levels, including palmitate that can be nutritionally available. Therefore, tumor growth is specifically susceptible to regulation of VLCFAs. We further demonstrate that VLCFA deficiency results in a significant decrease in ceramides as well as downstream glucosylceramides and sphingomyelins, which impairs mitochondrial morphology and renders cancer cells sensitive to oxidative stress and cell death. Taken together, our study highlights that VLCFAs are selectively required for cancer cell survival and reveals a potential strategy to suppress tumor growth.

Topics: Fatty Acids; Humans; Mitochondria; Neoplasms; Palmitates; Stearates

Topics: Carnitine O-Palmitoyltransferase; Cellular Senescence; Humans; Metabolic Flux Analysis; Neoplasms; Oleic Acid; Stearates

Biomimetic design has been extensively investigated. The only FDA-approved biomimetic albumin-bound paclitaxel may not be beneficial to some treated patients due to rapid dissociation upon intravenous infusion and no substantial improvement in the drug's pharmacokinetics or biodistribution. Herein, we developed an alternative and injectable preformed albumin-bound anticancer drug delivery. We combined HSA, Kolliphor HS 15 (HS15), and pirarubicin (THP) via purely physical forces in a thin-film hydration method to obtain an albumin-bound complex of HSA-THP. The lack of any chemical reactions preserves HSA bioactivity, in contrast to the destroyed secondary structure within AN-THP (albumin nanoparticle of THP) for the harsh manipulation during preparation. In vitro, HSA-THP showed a significantly higher cellular uptake efficiency than THP, and the complex was more cytotoxic. In vivo, HSA-THP showed longer half-life than THP. It also exhibited greater tumor accumulation and tumor penetration via gp60- and SPARC-mediated biomimetic transport than THP and AN-THP. As a result, HSA-THP showed strong antitumor and antimetastasis efficacy, with relatively little toxicity. These results suggest the clinical potential of biomimetic tumor-targeted drug delivery.

Topics: Albumins; Animals; Antineoplastic Agents; Cell Line, Tumor; Doxorubicin; Drug Carriers; Drug Delivery Systems; Female; Humans; Male; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Neoplasms; Polyethylene Glycols; Rats; Rats, Sprague-Dawley; Stearates

A novel hyaluronic acid modified transfersome was prepared to deliver drugs to lymphatics through the transdermal route. Doxorubicin loaded HA-GMS-T was able to efficiently penetrate into the deep skin tissue, leading to enhanced absorption by lymphatics. Most importantly, hyaluronic acid effectively improved the uptake of drug loaded nanocarriers by tumor cells.

Topics: Administration, Cutaneous; Animals; Antibiotics, Antineoplastic; Cell Line; Doxorubicin; Glycerol; Hyaluronic Acid; Liposomes; Liver; Lymphatic System; MCF-7 Cells; Mice; Nanoparticles; Neoplasms; Rats, Wistar; Skin; Skin Absorption; Stearates

Two kinds of thermally responsive polymers P(FAA-NIPA-co-AAm-co-ODA) and P(FPA-NIPA-co-AAm-co-ODA) containing folate, isopropyl acrylamide and octadecyl acrylate were fabricated through free radical random copolymerization for targeted drug delivery. Then the micelles formed in aqueous solution by self-assembly and were characterized in terms of particle size, lower critical solution temperature (LCST) and a variety of optical spectra. MTT assays demonstrated the low cytotoxicity of the control micelle and drug-loaded micelle on A549 cells and Bel 7402 cells. Then fluorescein and cypate were used as model drugs to optimize the constituents of micelles for drug entrapment efficiency and investigate the release kinetics of micelles in vitro. The FA and thermal co-mediated tumor-targeting efficiency of the two kinds of micelles were verified and compared in detail at cell level and animal level, respectively. These results indicated that the dual-targeting micelles are promising drug delivery systems for tumor-targeting therapy.

Topics: Acrylates; Cell Line, Tumor; Drug Carriers; Drug Evaluation, Preclinical; Folic Acid; Humans; Micelles; Molecular Imaging; Molecular Targeted Therapy; Neoplasms; Polyethylene Glycols; Polymers; Stearates; Temperature

The fluorescence-labeled closo-dodecaborane lipid (FL-SBL) was synthesized from (S)-(+)-1,2-isopropylideneglycerol as a chiral starting material. FL-SBL was readily accumulated into the PEGylated DSPC liposomes prepared from DSPC, CH, and DSPE-PEG-OMe by the post insertion protocol. The boron concentrations and the fluorescent intensities of the FL-SBL-labeled DSPC liposomes increased with the increase of the additive FL-SBL, and the maximum emission wavelength of the liposomes appeared at 531 nm. A preliminary in vivo imaging study of tumor-bearing mice revealed that the FL-SBL-labeled DSPC liposomes were delivered to the tumor tissue but not distributed to hypoxic regions.

Topics: Animals; Boron; Boron Compounds; Drug Delivery Systems; Female; Fluorescence; Liposomes; Mice; Neoplasms; Oxadiazoles; Phosphatidylcholines; Phosphatidylethanolamines; Polyethylene Glycols; Stearates; Tissue Distribution

The toxicity of sodium stearoyl lactylate (SSL) was examined in Wistar rats fed diets containing 0, 1.25, 2.5, and 5% SSL for one year, equivalent to mean daily intakes of 558, 1115, and 2214 mg/kg/day in males and 670, 1339, and 2641 mg/kg/day in females, respectively. SSL was well tolerated at these dietary levels as evidenced by the absence of toxicologically significant changes in the general condition and appearance of the rats, survival, neurobehavioral endpoints, growth, feed and water intake, ophthalmoscopic examinations, hematology and clinical chemistry parameters, urinalysis, or necropsy findings. The occurrence of uterine endometrial stromal polyps was the only finding of potential significance. Given the frequent occurrence of these benign tumors in rats, wide variability in the reported incidence of this type of polyps in rats, the lack of statistical significance and lack of biological evidence to suggest a mechanism for the slightly greater incidence in the groups fed 2.5 and 5% SSL, it was concluded that the endometrial stromal polyps observed in females fed SSL were not related to treatment. The no observed adverse effect level (NOAEL) of SSL was placed at 5%, the highest dietary level tested (equivalent to 2214 mg/kg/day for males and 2641 mg/kg/day for females).

Topics: Animals; Body Weight; Carcinogenicity Tests; Dose-Response Relationship, Drug; Drinking; Eating; Emulsions; Endometrial Stromal Tumors; Female; Leukocyte Count; Male; Neoplasms; No-Observed-Adverse-Effect Level; Rats; Rats, Inbred F344; Sex Characteristics; Stearates; Survival; Urinalysis