Comparative Analysis of the Antitumor Activity of Cis- and Trans-Resveratrol in Human Cancer Cells with Different p53 Status

Resveratrol, a natural plant phytoalexin, is produced in response to fungal infection or− UV irradiation. It exists as an isomeric pair with cis- and trans-conformation. Whereas multiple physiological effects of the trans-form, including a pronounced anti-tumoral activity, are nowadays elucidated, much less knowledge exists concerning the cis-isomer. In our work, we analyzed the antiproliferative and cytotoxic properties of cis-resveratrol in four different human tumor entities in direct comparison to trans-resveratrol. We used human cell lines as tumor models for hepatocellular carcinoma (HCC; HepG2, Hep3B), colon carcinoma (HCT-116, HCT-116/p53^(−/−)), pancreatic carcinoma (Capan-2, MiaPaCa-2), and renal cell carcinoma (A498, SN12C). Increased cytotoxicity in all investigated tumor cells was observed for the trans-isomer. To verify possible effects of the tumor suppressor p53 on resveratrol-induced cell death, we used wild type and p53-deleted or -mutated cell lines for every tested tumor entity. Applying viability and cytotoxicity assays, we demonstrated a differential, dose-dependent sensitivity towards cis- or trans-resveratrol among the respective tumor types.     

Colorectal Adenocarcinoma Cell Culture in a Microfluidically Controlled Environment with a Static Molecular Gradient of Polyphenol

To study the simultaneous effect of the molecular gradient of polyphenols (curcumin, trans-resveratrol, and wogonin) and biological factors released from tumor cells on apoptosis of adjacent cells, a novel microfluidic system was designed and manufactured. The small height/volume of microfluidic culture chambers and static conditions allowed for establishing the local microenvironment and maintaining undisturbed concentration profiles of naturally secreted from cells biochemical factors. In all trials, we observe that these conditions significantly affect cell viability by stimulating cell apoptosis at lower concentrations of polyphenols than in traditional multiwell cultures. The observed difference varied between 20.4–87.8% for curcumin, 11.0–37.5% for resveratrol, and 21.7–62.2% for wogonin. At low concentrations of polyphenols, the proapoptotic substances released from adjacent cells, like protein degradation products, significantly influence cell viability. The mean increase in cell mortality was 38.3% for microfluidic cultures. Our research has also confirmed that the gradient microsystem is useful in routine laboratory tests in the same way as a multiwell plate and may be treated as its replacement in the future. We elaborated the new repetitive procedures for cell culture and tests in static gradient conditions, which may become a gold standard of new drug investigations in the future.     

Solubilization of Trans-Resveratrol in Some Mono-Solvents and Various Propylene Glycol + Water Mixtures

This research deals with the determination of solubility, Hansen solubility parameters, dissolution properties, enthalpy–entropy compensation, and computational modeling of a naturally-derived bioactive compound trans-resveratrol (TRV) in water, methanol, ethanol, n-propanol, n-butanol, propylene glycol (PG), and various PG + water mixtures. The solubility of TRV in six different mono-solvents and various PG + water mixtures was determined at 298.2–318.2 K and 0.1 MPa. The measured experimental solubility values of TRV were regressed using six different computational/theoretical models, including van’t Hoff, Apelblat, Buchowski–Ksiazczak λh, Yalkowsly–Roseman, Jouyban–Acree, and van’t Hoff–Jouyban–Acree models, with average uncertainties of less than 3.0%. The maxima of TRV solubility in mole fraction was obtained in neat PG (2.62 × 10⁻²) at 318.2 K. However, the minima of TRV solubility in the mole fraction was recorded in neat water (3.12 × 10⁻⁶) at 298.2 K. Thermodynamic calculation of TRV dissolution properties suggested an endothermic and entropy-driven dissolution of TRV in all studied mono-solvents and various PG + water mixtures. Solvation behavior evaluation indicated an enthalpy-driven mechanism as the main mechanism for TRV solvation. Based on these data and observations, PG has been chosen as the best mono-solvent for TRV solubilization.     

反式白藜芦醇热稳定性与光致异构化的高效液相色谱和液相色谱-电喷雾离子化质谱研究

应用高效液相色谱(HPLC)及液相色谱-电喷雾离子化质谱(LC-ESI-MS)方法对反式白藜芦醇的长期热稳定性及光致顺反异构化反应进行了研究。色谱条件为:采用Hypersil-ODS色谱柱分离,流动相为甲醇-0.05%三氟乙酸水溶液(体积比为60∶40)(用于HPLC分析)及甲醇-5 mmol/L甲酸铵水溶液(含0.1%甲酸)（体积比为60∶40)(用于LC-ESI-MS分析),检测波长300 nm,进样量20　μL(HPLC)或10 μL(LC-ESI-MS);质谱检测中设定为负离子模式。在4~40     

反式白藜芦醇双功能单体印迹固相萃取柱的制备及应用

采用自组装技术,分别以β-环糊精和甲基丙烯酸为功能单体,反式白藜芦醇为模板分子,乙二醇二甲基丙烯酸酯为交联剂,制备了一种双功能单体印迹聚合物。 并将其作为固相萃取材料萃取红酒和白酒酒样中的反式白藜芦醇。 结果表明,与单功能印迹材料和非印迹材料相比,这种双功能单体印迹材料具有更高的吸附容量和选择性;结合高效液相色谱,建立了酒样中反式白藜芦醇浓度的检测方法。 该方法的线性范围在0.003~2 mg/L,红酒的回收率在87.9%~93.2%,白酒的回收率在89.3%~91.2%,检测限为0.001 mg/L。     

Sunscreens Containing Cyclodextrin Inclusion Complexes for Enhanced Efficiency: A Strategy for Skin Cancer Prevention

Unprotected exposure of skin to solar ultraviolet radiation (UVR) may damage the DNA of skin cells and can lead to skin cancer. Sunscreens are topical formulations used to protect skin against UVR. The active ingredients of sunscreens are UV filters that absorb, scatter, and/or reflect UVR. Preventing the formation of free radicals and repairing DNA damages, natural antioxidants are also added to sunscreens as a second fold of protection against UVR. Antioxidants can help stabilise these formulations during the manufacturing process and upon application on skin. However, UV filters and antioxidants are both susceptible to degradation upon exposure to sunlight and oxygen. Additionally, due to their poor water solubility, natural antioxidants are challenging to formulate and exhibit limited penetration and bioavailability in the site of action (i.e., deeper skin layers). Cyclodextrins (CDs) are cyclic oligosaccharides that are capable of forming inclusion complexes with poorly soluble drugs, such as antioxidants. In this review, we discuss the use of CDs inclusion complexes to enhance the aqueous solubility of antioxidants and chemical UV filters and provide a protective shield against degradative factors. The role of CDs in providing a controlled drug release profile from sunscreens is also discussed. Finally, incorporating CDs inclusion complexes into sunscreens has the potential to increase their efficiency and hence improve their skin cancer prevention.     

Characterization of Wines by Trans-Resveratrol Concentration: A Case Study of Romanian Varieties

The goal of this study was to determine the trans-resveratrol concentration in wine. A set of 70 wine samples from Romania, produced according to the appellation of origin system, were analyzed by reverse-phase high performance liquid chromatography. White wines were found to have markedly lower concentrations of trans-resveratrol in comparison with red wines. The values were between 0.025 to 10.23 mg/L for red wine and from 0.074 to 2.572 mg/L for white wine. Red wine is a good dietary source of resveratrol.     

Fabrication of novel Ag/g-C3N4 electrode for resveratrol sensors

Ag/g-C₃N₄ is fabricated and used as an electrode for determining trans-resveratrol concentration. The compositional and structural characteristics of the as-fabricated Ag/g-C₃N₄ are studied through X-ray diffraction, transmission electron microscopy, and energy dispersive spectroscopy. Additionally, the electrochemical behavior of Ag/g-C₃N₄ is investigated using cyclic voltammetry. According to the experimental results, 1 wt%Ag/g-C₃N₄ exhibits an oxidation peak at 0.48 V, with a low detection limit (1.88 × 10⁻⁷ M) and satisfactory correlation coefficient (0.9975), suggesting that the proposed Ag/g-C₃N₄ electrode can be successfully used for detecting trans-resveratrol.