Human immunodeficiency virus (HIV) infection is associated with B-cell malignancies in patients though HIV-1 is not able to infect B-cells. The rate of B-cell lymphomas in HIV-infected individuals remains high even under the combined antiretroviral therapy (cART) that reconstitutes the immune function. Thus, the contribution of HIV-1 to B-cell oncogenesis remains enigmatic. HIV-1 induces oxidative stress and DNA damage in infected cells via multiple mechanisms, including viral Tat protein. We have detected elevated levels of reactive oxygen species (ROS) and DNA damage in B-cells of HIV-infected individuals. As Tat is present in blood of infected individuals and is able to transduce cells, we hypothesized that it could induce oxidative DNA damage in B-cells promoting genetic instability and malignant transformation. Indeed, incubation of B-cells isolated from healthy donors with purified Tat protein led to oxidative stress, a decrease in the glutathione (GSH) levels, DNA damage and appearance of chromosomal aberrations. The effects of Tat relied on its transcriptional activity and were mediated by NF-κB activation. Tat stimulated oxidative stress in B-cells mostly via mitochondrial ROS production which depended on the reverse electron flow in Complex I of respiratory chain. We propose that Tat-induced oxidative stress, DNA damage and chromosomal aberrations are novel oncogenic factors favoring B-cell lymphomas in HIV-1 infected individuals.
This work demonstrates the interest of new bio composite materials for the elimination of pharmaceuticals (diclofenac (DCF), carbamazepine (CBZ) and sulfamethoxazole (SMX)) from aqueous solution. The synthesized materials are based on activated carbon (ACP) of Argania Spinosa tree nutshells by calcination and H 3 PO 4 activation, and commercial TiO 2 (Degussa P25). AC/TiO 2 composite materials wereprepared by temperature impregnation with different TiO 2 mass ratio (9, 16.6 and 33.3%). Characterization of AC and AC/TiO 2 revealed remarkable adsorption properties of bio sourced AC (BET surface area of 1159 m 2 /g) and successful deposition of layer of TiO 2 on AC surface in controlled amount, with some physical changes (surface area and total pore volume decrease). Langmuir model describes efficiently adsorption of pharmaceuticals onto AC/TiO 2 with maximum capacities of 153.8, 105.3 and 125.0 mg/g at 25°C with 9% of TiO 2 (AC/TiO 2 -9%) for DCF, CBZ and SMX, respectively. Photocatalytic activities of all composites were validated on CBZ. The elimination efficiency of relative high concentration of pharmaceuticals (50 mg/L) were proved with disappearances in the range of 50-100% after six hours upon simulated solar irradiation with the most interesting material AC/TiO 2 -9% at a concentration of 0.1 g/L.
Cancer stem cells (CSCs), including those of advanced prostate cancer, are a suggested reason for tumor resistance toward conventional tumor therapy. Therefore, new therapeutic agents are urgently needed for targeting CSCs. Despite the minimal understanding of their modes of action, natural products and herbal therapies have been commonly used in the prevention and treatment of many cancers. Berberis libanotica Ehrenb (BLE) is a plant rich in alkaloids which may possess anti-cancer activity and a high potential for eliminating CSCs. We tested the effect of BLE on prostate cancer cells and our data indicated that this extract induced significant reduction in cell viability and inhibited the proliferation of human prostate cancer cell lines (DU145, PC3 and 22Rv1) in a dose- and time-dependent manner. BLE extract induced a perturbation of the cell cycle, leading to a G0-G1 arrest. Furthermore, we noted 50% cell death, characterized by the production of high levels of reactive oxidative species (ROS). Inhibition of cellular migration and invasion was also achieved upon treatment with BLE extract, suggesting a role in inhibiting metastasis. Interestingly, BLE extract had a major effect on CSCs. Cells were grown in a 3D sphere-formation assay to enrich for a population of cancer stem/progenitor cells. Our results showed a significant reduction in sphere formation ability. Three rounds of treatment with BLE extract were sufficient to eradicate the self-renewal ability of highly resistant CSCs. In conclusion, our results suggest a high therapeutic potential of BLE extract in targeting prostate cancer and its CSCs.
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