In vitro cytotoxicity of curcuminoids against head and neck cancer HNO97 cell line

Oral squamous cell carcinoma (OSCC) is a malignant tumour of Head and Neck Cancer (HNC). The recent therapeutic approaches used to treat cancer have adverse side effects. The natural agents exhibiting anticancer activities are generally considered to have a robust therapeutic potential. Curcuminoids, one of the major active compounds of the turmeric herb, are used as a therapeutic agent for several diseases including cancer. In this study, the cytotoxicity of curcuminoids was investigated against OSCC cell line HNO97. Our data showed that curcuminoids significantly inhibits the proliferation of HNO97 in a time and dose-dependent manner (IC50=35 μM). Cell cycle analysis demonstrated that curcuminoids increased the percentage of G2/M phase cell populations in the treated groups. Treating HNO97 cells with curcuminoids led to cell shrinking and increased detached cells, which are the typical appearance of apoptotic cells. Moreover, flow cytometry analysis revealed that curcuminoids significantly induced apoptosis in a time-dependent manner. Furthermore, as a response to curcuminoids treatment, comet tails were formed in cell nuclei due to the induction of DNA damage. Curcuminoids treatment reduced the colony formation capacity of HNO97 cells and induced morphological changes. Overall, these findings demonstrate that curcuminoids can in vitro inhibit HNC proliferation and metastasis and induce apoptosis.

Antioxidant and Anticancer Activities and Protein Interaction of the Oxidovanadium(IV) Naringin Complex

The complex of oxidovanadium(IV) with naringin (Narg) [VO(Narg)2] 8H2O (VONarg) was prepared according to the literature improving the synthetic procedure and physicochemical characterization. In addition, biological activities (cytotoxic, antioxidant, and BSA interaction) were determined. The metal coordinated through the 5-hydroxy and 4-carbonyl groups of rings A and C of naringin, respectively. The antioxidant activity of VONarg, determined in vitro, was higher than those of the flavonoid against superoxide and peroxyl reactive oxygen species (ROS) and DPPH radical. The cytotoxic properties were determined by a MTT assay on adenocarcinoma human alveolar basal epithelial cells (A549). VONarg exerted a 20% decrease in cancer cells viability at 24 h incubation, while naringin and oxidovanadium(IV) cation did not show cytotoxicity. Measurements with the normal HEK293 cell line showed that the inhibitory action of the complex is selective. VONarg generated intracellular reactive oxygen species (ROS), depletion of reduced glutathione and depolarization of mitochondrial membrane potential, typical for apoptotic pathway, producing cell death by oxidative stress mechanism. Moreover, naringin interacted with bovine serum albumin (BSA) through hydrophobic interactions in a spontaneous process, and VONarg showed greater affinity for the protein but can still be transported and delivered by it (Ka 104 L·mol−1 order).

Wonderful Natural Drugs with Surprising Nutritional Values, Rheum Species, Gifts of the Nature

Nutrition therapy on the basis of traditional medicinal plants and herbs is common in many Asian countries, especially Iran and China. Rheum species, especially rhubarbs, belong to plant medicines recognized in 2500 BC. An online search of the literature was carried out at Pubmed/Medline, Scopus, and Google scholar, covering all years until April 2021. The following key terms were used, usually in combinations: Rheum species, rhubarb, natural products, pharmaceutical benefits, anthraquinones and anthranone. After performing the literature search, the bibliographies of all articles were checked for cross-references that were not found in the search databases. Articles were selected if they reported any biological effects, ethnomedicinal uses, phytochemical compounds and botanical description of Rheum species. The most important components of rhubarb are anthraquinones, anthranone, stilbenes, tannins and butyrophenones. Anthraquinones consist of rhein, emodin, aloe-emodin and chrysophanl, and anthranone includes sennosides and rheinosides. The most important health benefits of rhubarb are antioxidant and anticancer activities, antimicrobial activity, wound healing action, hepatoprotective and anti-diabetic effects, and nephroprotective effect, as well as anti-inflammatory, analgesic and antibacterial activities. Integration of both traditional pharmaceutical science and modern medicines may promote sustainability, lead to organic life and promote the cultivation of medicinal plants.

Mangostanin, a Xanthone Derived from Garcinia mangostana Fruit, Exerts Protective and Reparative Effects on Oxidative Damage in Human Keratinocytes

The fruit of Garcinia mangostana (mangosteen) is known in ancient traditional Asian medicine for its antioxidant, anti-inflammatory, immunomodulatory and anticancer activities. These effects are mainly due to the action of polyphenols known as xanthones, which are contained in the pericarp of the fruit. In recent years, there has been a growing interest from pharmaceutical companies in formulating new topicals based on mangosteen full extracts to prevent skin aging. However, the molecules responsible for these effects and the mechanisms involved have not been investigated so far. Here, the arils and shells of Garcinia mangostana were extracted with chloroform and methanol, and the extracts were further purified to yield 12 xanthone derivatives. Their effects were evaluated using in vitro cultures of human epidermal keratinocytes. After confirming the absence of cytotoxicity, we evaluated the antioxidant potential of these compounds, identifying mangostanin as capable of both protecting and restoring oxidative damage induced by H2O2. We showed how mangostanin, by reducing the generation of intracellular reactive oxygen species (ROS), prevents the activation of AKT (protein kinase B), ERK (extracellular signal-regulated kinase), p53, and other cellular pathways underlying cell damage and apoptosis activation. In conclusion, our study is the first to demonstrate that mangostanin is effective in protecting the skin from the action of free radicals, thus preventing skin aging, confirming a potential toward its development in the nutraceutical and cosmeceutical fields.

Coordination-assembled Nanoarchitectonics of Antioxidant Peptide and Flavonoid Myricetin for Sustainably Scavenging Free Radicals

Oxidative stress can lead to permanent and irreversible damage for cellular components, and even cause cancer and many diseases. Therefore, the development of antioxidative reagents is a significant strategy for alleviating chronic diseases and maintaining the redox balance. Small-molecule bioactive compounds have exhibited huge therapeutic potential in antioxidant and anti-inflammatory. Myricetin (Myr) as well-defined natural flavonoid, has drawn wide attention on highly effective antioxidant, anti-inflammatory, antimicrobial, and anticancer activities. Especially at antioxidation, Myr is capable of not only chelating intracellular transition metal ions for removing reactive oxygen species (ROS), but also activating antioxidant enzymes and related signal, achieving sustainable scavenging radical activity. However, Myr possesses poor water solubility, which limits its bioavailability for biomedical application, even clinical therapeutic potential. The endogenous antioxidant peptide glutathione (GSH) plays a direct role on antioxidant in cells and possesses good hydrophilicity and biocompatibility, but is easily metabolized by enzyme. To take advantages of their antioxidation activity and overcome the above-mentioned limitations, the GSH, Zn2+ and Myr are selected to co-assemble into Myr-Zn2+-GSH (abbreviated as MZG nanoparticles or nanoarchitectonics). Thence, this study offers a new design to harness stable, sustainable antioxidant nanoparticles with high loading capacity and bioavailability, good biocompatibility for optimizing antioxidant to protect cells from oxygenated damage.

Synthetic prodrug design enables biocatalytic activation in mice to elicit tumor growth suppression

Considering the intrinsic toxicities of transition metals, their incorporation into drug therapies must operate at minimal amounts while ensuring adequate catalytic activity within complex biological systems. As a way to address this issue, this study investigates the design of synthetic prodrugs that are not only tuned to be harmless, but can be robustly transformed in vivo to reach therapeutically relevant levels. To accomplish this, retrosynthetic prodrug design highlights the potential of naphthylcombretastatin-based prodrugs, which form highly active cytostatic agents via sequential ring-closing metathesis and aromatization. Structural adjustments will also be done to improve aspects related to catalytic reactivity, intrinsic bioactivity, and hydrolytic stability. The developed prodrug therapy is found to possess excellent anticancer activities in cell-based assays. Furthermore, in vivo activation by intravenously administered glycosylated artificial metalloenzymes can also induce significant reduction of implanted tumor growth in mice.

Melatonin Induces Cell Cycle Arrest, Inhibits Cell Proliferation and Accelerates Apoptosis by Modulation of CDK4 in NSCLC

Purpose To explore whether melatonin affect the progression of cell cycle and exert anticancer activities via the modulation of CDK4 in NSCLC . Methods Cells treated with melatonin were used for assessing the anticancer effect of melatonin. Cells transfected with lentivirus for CDK4 upregulation or downregulation was constructed to evaluate the role of CDK4 in melatonin-induced anticancer effect. The protein and mRNA level of CDK4, PCNA and Bax were detected by western blotting and qRT-PCR. The application of flow cytometry was used for analyzing the distribution of cell cycle and apoptosis. Animal model of subcutaneous tumor was constructed and used for further study in vivo. Results We found that melatonin inhibited cell viability, colony formation, downregulated the expression of CDK4 and PCNA while upregulated the level of Bax. Besides, melatonin decreased the phosphorylation of ERK. Importantly, inhibition of ERK activation by PD98059 particapated in melatonin-induced downregulation of CDK4. Furthermore, melatonin led to G1 arrest and cell apoptosis. CDK4 knockdown enhanced melatonin-induced cell cycle arrest while CDK4 overexpression reversed the effect. Additionally, the animal experiment showed that melatonin decreased the level of CDK4 and inhibited tumor growth. However, the anti-tumor effect of melatonin was reversed by CDK4 overexpression. Conclusion Taken together, CDK4 involved in anti-cancer activities of melatonin. Melatonin led to G1 arrest, blocked G1-to-S transition, as a result, inhibited cell proliferation and accelerates apoptosis via suppressing CDK4 signaling. Targeting CDK4 inhibition and combining it with melatonin has protential to be a novel strategy for NSCLC.