Functionalization of poly(3‐hydroxybutyrate) with different thiol compounds inhibits MDM2–p53 interactions in MCF7 cells

Abstract

High-molecular-weight poly(3-hydroxybutyrate) (PHB) has a low reactivity toward its terminal functional groups. Thus, the chemical reactivity of PHB was enhanced by the chemical degradation that occurred via β-elimination through the functionalization of PHB with ethylene glycol to give a low-molecular-weight PHB-diol. The reaction of PHB-diol with acryloyl chloride gave PHB-diacrylate, which was grafted by thiol compounds, such as ethane dithiol, 2-mercaptoethanol, ethane thiol, dithiothreitol, butane thiol, and thioglycolic acid, via a Michael-type addition reaction. The chemical and thermal properties of the functionalized PHB-thiol products were characterized with Fourier transform infrared spectroscopy, 1 H-NMR, gel permeation chromatography, differential scanning calorimetry, and thermogravimetric analysis techniques. X-ray diffraction showed that the PHB-thiol polymers had slight differences in crystallinity compared with neat PHB. The biological activities of the neat polymer and new PHB-thiol polymers, including the antibacterial and anticancer activities, were tested, and some of these products showed antibacterial and anticancer activities. These anticancer activities were attributed to the ability of these PHB-thiol polymers to induce apoptosis (as revealed by the higher expression of Bax and caspase 9 and the lower expression of Bcl2) and cell-cycle arrest in the G0/G1 phase, which is associated with the higher expression of p53 and p21 and the lower expression of the p53 inhibitor, MDM2. Thus, the anticancer effect of these PHB-thiol polymers may have been due to their ability to inhibit MDM2-p53 interactions.

Panax ginseng modulates oxidative stress, DNA damage, apoptosis, and inflammations induced by silicon dioxide nanoparticles in rats

“…Flow cytometry was applied to detect the influence of various treatments on cell number of each phase of the cell cycle as performed previously with some modifications. 34 Briefly, freshly dissected liver tissues were lysed by collagenase enzyme (0.1%, Invitrogen), then mesh filtered (0.7 mm nylon) and centrifuged (4000 rpm/5 min). After fixation, the cells were stained using propidium iodide and analyzed by Attune flow cytometer (Applied Bio-system).…”

Poly(3-hydroxybutyrate)/poly(amine)-coated nickel oxide nanoparticles for norfloxacin delivery: antibacterial and cytotoxicity efficiency

“…Poly(3-hydroxybutyrate) (PHB) are the most thoroughly studied forms of biopolymer polyesters family for biomedical applications due to their biocompatibility, biodegradability, nontoxic, and adjustable mechanical properties. 18,19 These properties make PHB as an ideal candidate in medicine, surgery, pharmacology and in tissue engineering scaffolds. It was reported that PHB nanoparticles acted as an efficient carrier vehicle for doxorubicin drug and delayed the release for 5-7 days.…”

The Microbial Production of Polyhydroxyalkanoates from Waste Polystyrene Fragments Attained Using Oxidative Degradation

“…Currently, PHAs are being used either as a blend or in its pure form in a variety of applications; scl-PHAs (short chain length) are predominantly used to produce food packaging and disposable items, and mcl-PHAs (medium chain length-characterized as elastomers) are appropriate for high value-added applications, such as surgical stitching, implants, and drug delivery systems [5,7,8]. There is also the opportunity to functionalize PHB chemically and/or enzymatically (as discussed later), which is among one of the most impervious polymers to be processed in certain plastic items [9]. Global use and industrialization of PHAs is limited due to high production costs, which results in higher prices than petrol-based polymers, such as polypropylene (PP) or polyethylene (PE), that have a price of approximately US $0.60–0.87/lb [10,11].…”