Oxidative Stress and Multi-Organel Damage Induced by Two Novel Phytocannabinoids, CBDB and CBDP, in Breast Cancer Cells

Over the last few years, much attention has been paid to phytocannabinoids derived from Cannabis for their therapeutic potential. Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are the most abundant compounds of the Cannabis sativa L. plant. Recently, novel phytocannabinoids, such as cannabidibutol (CBDB) and cannabidiphorol (CBDP), have been discovered. These new molecules exhibit the same terpenophenolic core of CBD and differ only for the length of the alkyl side chain. Roles of CBD homologs in physiological and pathological processes are emerging but the exact molecular mechanisms remain to be fully elucidated. Here, we investigated the biological effects of the newly discovered CBDB or CBDP, compared to the well-known natural and synthetic CBD (nat CBD and syn CBD) in human breast carcinoma cells that express CB receptors. In detail, our data demonstrated that the treatment of cells with the novel phytocannabinoids affects cell viability, increases the production of reactive oxygen species (ROS) and activates cellular pathways related to ROS signaling, as already demonstrated for natural CBD. Moreover, we observed that the biological activity is significantly increased upon combining CBD homologs with drugs that inhibit the activity of enzymes involved in the metabolism of endocannabinoids, such as the monoacylglycerol lipase (MAGL) inhibitor, or with drugs that induces the activation of cellular stress pathways, such as the phorbol ester 12-myristate 13-acetate (PMA).

Chemical Compositions of the Essential Oil Extracted from the Seeds of Garcina Kola, and Its Biological Activities

The essential oil was obtained from the seeds of Garcina kola and its compositions were investigated by GC-MS and ICP-MS, respectively. 74 organic compounds and 9 trace elements beneficial to human health were confirmed in this oil. Then, the in vitro antioxidant and anticancer activities were evaluated accordingly. The results showed that this essential oil exhibited stronger antioxidant activity against DPPH⸱ with the scavenging rate of 94.19% at 0.2 mg/mL, as well as potent inhibition against gastric cancer, lung cancer(A549) and Hela cell lines with the inhibitions of 96.397%±0.929, 98.005%±0.513 and 94.77±2.09 respectively at 8.3 mg/mL. While it exhibited moderate inhibition against the human breast carcinoma cells (MCF-7) with the inhibition of 59.257%±4.544 at 8.3mg/mL. In consideration of Garcina kola being consumed in Nigeria for a long time, this essential oil obtained from the Garcina kola can be used in the field of food, cosmetic or drugs.

Design, Synthesis and Evaluation of Hybrid 2-Heteroaryl BenzimidazoleChalcone Derivatives as Anticancer Agents

: A series of 2-heteroaryl benzimidazole-chalcone hybrids were synthesized and the anticancer activity was estimated by MTT assay in human breast, lung, colon, and ovarian cancer cell lines. The biological results indicate that the compounds showed good anticancer activity with a range of IC50 values 0.056-19.5 µM. Compound 11b with hexa methoxy groups, bearing three methoxy groups on each terminal aryl ring exhibited a significant IC50 value (56 nM) against human breast carcinoma cells, which is 37 times higher potency in comparison with the reference Etoposide. Further compounds substituted variably with methoxy and nitro groups on the phenyl ring of chalcone showed more promising anticancer activity than the compounds with unsubstituted phenyl ring or variably alkyl-substituted phenyl ring of chalcone. The molecular docking results indicate that the synthesized compounds bind in the active site of Abl tyrosine kinase, the target of anticancer drug Imatinib. The present study provides the synergistic effect of hybrids, benzimidazole-chalcones as potential anticancer agents and will aid in the discovery of new anticancer agents.

Chitosan of Peppery Milky Cap Fungi (Lactarius Pergamenus (Fr.) Fr): Isolation, Study of Physico-Chemical Properties and Biological Activity

Chitosan is widely used in biology and medicine. Usually, it is isolated from chitin of crustaceans, while chitosan of the basidiomycetes fungi is poorly studied. The purpose of this study was: 1) to develop a method for isolation of chitosan from dried pomace of the peppery milky cap (Lactarius pergamenus); 2) to study of physico-chemical and biological properties of the isolated chitosan. As tradicionally, chitosan was obtained by the alkaline hydrolysis of chitin. The determination of its molecular mass was performed using the viscometric method and further analyzed by disk electrophoresis (pH 5.0). The anti-microbial and cytotoxic activities were measured spectrophoto�metrically as a convertion of MTT dye to formazan, while the antifungal activity was evaluated using by counting colony-forming units (CFU). Chitosan of L. pergamenus fungi was shown to have lower molecular mass and a lower degree of deacetylation compared to shrimp chitosan. A yield of chitosan from a pomace of L. pergamenus was 6.27%. A heterogeneous product was obtained with an average molecular mass of 72 kDa and a degree of deacetylation equal - 87.1%. In 10 mg/ml dose, it inhibited by 29% the growth of gram-positive of Staphylococcus aureus (ATCC25923) bacteria and inhibited growth of gram-negative Echerichia coli dH5a - by 86% and Pseudomonas aeruginosa (ATCC9027) bacteria by 55%. Approximately 50 and 90 % of Candida albicans (pat.) cells were killed at the action of chitosan in doses of 0.025 mg/mL and 0.1 mg/mL correspondingly. It should be noted that this chitosan preparation did not affect a growth of human embryonic kidney pseudonormal cells of HEK 293 line and human breast carcinoma cells of MCF7 line.

Ionizing Radiation-induced Proteomic Oxidation in Escherichia coli

Recent work has begun to investigate the role of protein damage in cell death because of ionizing radiation (IR) exposure, but none have been performed on a proteome-wide basis, nor have they utilized MS (MS) to determine chemical identity of the amino acid side chain alteration. Here, we use Escherichia coli to perform the first MS analysis of IR-treated intact cells on a proteome scale. From quintuplicate IR-treated (1000 Gy) and untreated replicates, we successfully quantified 13,262 peptides mapping to 1938 unique proteins. Statistically significant, but low in magnitude (<2-fold), IR-induced changes in peptide abundance were observed in 12% of all peptides detected, although oxidative alterations were rare. Hydroxylation (+15.99 Da) was the most prevalent covalent adduct detected. In parallel with these studies on E. coli, identical experiments with the IR-resistant bacterium, Deinococcus radiodurans, revealed orders of magnitude less effect of IR on the proteome. In E. coli, the most significant target of IR by a wide margin was glyceraldehyde 3′-phosphate dehydrogenase (GAPDH), in which the thiol side chain of the catalytic Cys residue was oxidized to sulfonic acid. The same modification was detected in IR-treated human breast carcinoma cells. Sensitivity of GAPDH to reactive oxygen species (ROS) has been described previously in microbes and here, we present GAPDH as an immediate, primary target of IR-induced oxidation across all domains of life.

Investigation of Silver Nitrate on Cytotoxicity and Apoptosis in MCF7 Human Breast Carcinoma Cells

Background: Metal compounds have been studied in vitro for many years and these compounds’s effects are shown on tumors. Anticancer potential of silver and silver metal compounds is investigated in these days. A study on the in vitro interactions of silver nitrate (AgNO3) with MCF7 human breast carcinoma cells was performed to detect cytotoxic effects which induce apoptotic pathways.Materials and Methods: The cytotoxicity of silver nitrate which administered on MCF7 cells was assessed by MTT assay. The apoptotic influences of silver nitrate (IC50: inhibition concentration) were determined using Annexin V-FITC/PI, JC-1, TUNEL paraffin embedded and confocal microscopy assays. Silver nitrate induced cytotoxicity and apoptosis in MCF7 cells. Results: In this work, we demonstrated that the inhibition of cell growth which is time and dose dependent in MCF7 cells for 24, 48 and 72 hours. The inhibition concentration of silver nitrate (IC50) was found as 10 µM in MCF7 cells for 72 hrs. The early/late apoptotic and necrotic changes which occured with silver nitrate (IC50: 10µM) administered, were analyzed in the MCF7 cells for 72 hrs. However, the reduced mitochondrial membrane activity (ΔΨmt) was observed by silver nitrate-treated (IC50: 10µM) in the MCF7 cells for 72 hrs. In addition to these findings, a variety of apoptotic structures were demonstrated on MCF7 cells for 72 hrs. Conclusions: The results suggest that silver nitrate could be attributed as chemotherapeutic agent for medical applications in breast cancer treatment.