scholarly journals Supramolecular Caffeic Acid and Bortezomib Nanomedicine: Prodrug Inducing Reactive Oxygen Species and Inhibiting Cancer Cell Survival

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1082
Author(s):  
Ludwig Erik Aguilar ◽  
Se Rim Jang ◽  
Chan Hee Park ◽  
Kang Min Lee

Phenolics from plant materials have garnered attention in nanomedicine research, due to their various medicinal properties. Caffeic acid, a phenolic compound that is abundant in coffee beans, has been proven to have anticancer effects, due to its reactive oxygen species (ROS)-inducing properties. Here, a supramolecular nanomedicine was designed using caffeic acid molecule and the synthetic anticancer drug bortezomib, via catechol–boronic acid conjugation and Fe(III) ion crosslinking. Bortezomib is a proteasome-inhibiting drug and its boronic acid functional group can bind to caffeic acid’s catechol moiety. By having a nanoparticle formulation that can deliver bortezomib via intracellular endocytosis, the catechol–boronic acid conjugation can be dissociated, which liberates the boronic acid functional group to bind to the 26S proteasome of the cell. The ROS-inducing property of caffeic acid also complements the bortezomib payload, as the latter suppresses the survival mechanism of the cell through NF-κB inhibition.

Author(s):  
Dumitriţa RUGINǍ ◽  
Adela PINTEA ◽  
Raluca PÂRLOG ◽  
Andreea VARGA

Oxidative stress causes biological changes responsible for carcinogenesis and aging in human cells. The retinal pigmented epithelium is continuously exposed to oxidative stress. Therefore reactive oxygen species (ROS) and products of lipid peroxidation accumulate in RPE. Neutralization of ROS occurs in retina by the action of antioxidant defence systems. In the present study, the protective effect of caffeic acid (3,4-dihydroxy cinnamic acid), a dietary phenolic compound, has been examined in normal and in oxidative stress conditions (500 µM peroxide oxygen) in cultures human epithelial pigment retinal cells (Nowak, M. et al.). The cell viability, the antioxidant enzymes activity (CAT, GPx, SOD) and the level of intracellular reactive oxygen species (ROS) were determined. Exposure to l00 µM caffeic acid for 24 h induced cellular changes indicating the protective effect of caffeic acid in RPE cells. Caffeic acid did not show any cytotoxic effect at concentrations lower than 200 μM in culture medium. Treatment of RPE cells with caffeic acid causes an increase of catalase, glutathione peroxidase and superoxide dismutase activity, especially in cells treated with hydrogen peroxide. Caffeic acid causes a decrease of ROS level in cells treated with hydrogen peroxide. This study proved that caffeic acid or food that contain high levels of this phenolic acid may have beneficial effects in prevention of retinal diseases associated with oxidative stress by improving antioxidant defence systems.


2020 ◽  
Vol 11 (22) ◽  
pp. 5735-5739 ◽  
Author(s):  
Eunhye Lee ◽  
Xingshu Li ◽  
Juwon Oh ◽  
Nahyun Kwon ◽  
Gyoungmi Kim ◽  
...  

A boronic acid functionalized phthalocyanine displays aggregation-enhanced reactive oxygen species (ROS) generation and excellent photodynamic antibacterial activity.


2018 ◽  
Vol 12 (20) ◽  
pp. 263-268 ◽  
Author(s):  
Brito Dantas Mariana ◽  
Lima Sampaio Tiago ◽  
Róseo Paula Pessoa Bezerra de Menezes Ramon ◽  
Magalhães Ferreira Jamile ◽  
Sousa Melo Tiago ◽  
...  

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 773
Author(s):  
Maribel Escoll ◽  
Diego Lastra ◽  
Natalia Robledinos-Antón ◽  
Francisco Wandosell ◽  
Inés María Antón ◽  
...  

Due to their high metabolic rate, tumor cells produce exacerbated levels of reactive oxygen species that need to be under control. Wiskott–Aldrich syndrome protein (WASP)-interacting protein (WIP) is a scaffold protein with multiple yet poorly understood functions that participates in tumor progression and promotes cancer cell survival. However, its participation in the control of oxidative stress has not been addressed yet. We show that WIP depletion increases the levels of reactive oxygen species and reduces the levels of transcription factor NRF2, the master regulator of redox homeostasis. We found that WIP stabilizes NRF2 by restraining the activity of its main NRF2 repressor, the E3 ligase adapter KEAP1, because the overexpression of a NRF2ΔETGE mutant that is resistant to targeted proteasome degradation by KEAP1 or the knock-down of KEAP1 maintains NRF2 levels in the absence of WIP. Mechanistically, we show that the increased KEAP1 activity in WIP-depleted cells is not due to the protection of KEAP1 from autophagic degradation, but is dependent on the organization of the Actin cytoskeleton, probably through binding between KEAP1 and F-Actin. Our study provides a new role of WIP in maintaining the oxidant tolerance of cancer cells that may have therapeutic implications.


2019 ◽  
Vol 17 (4) ◽  
pp. 401-405
Author(s):  
Yang Li-Chien ◽  
Lin David Pei-Cheng ◽  
Chang Han-Hsin ◽  
Tung Kwong-Chung

Oxygen supply is crucial to the health of avascular human cornea where low-oxygen-transmissible soft contact lenses often cause keratitis upon excessive wear time. Caffeic acid phenethyl ester, an active component of propolis, has anti-oxidative and anti-inflammatory properties. This study investigated the in vitro effects of caffeic acid phenethyl ester on corneal inflammation and its underlying action. We measured NF-κB activity and Dichloro-dihydro-fluorescein diacetate staining to demonstrate that caffeic acid phenethyl ester ameliorates hypoxia-induced inflammation of corneal endothelial cells and reactive oxygen species formation. The results may provide a new strategy to mitigate keratitis by caffeic acid phenethyl ester treatment.


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