Abstract
Plumbagin is a plant naphtoquinone exerting anti-cancer properties including apoptotic cell death induction and generation of reactive oxygen species (ROS). The aim of this study was to elucidate parameters explaining the differential leukemia cell sensitivity towards this compound. Among several leukemia cell lines, U937 monocytic leukemia cells appeared more sensitive to plumbagin treatment in terms of cytotoxicity and level of apoptotic cell death compared to more resistant Raji Burkitt lymphoma cells. Moreover, U937 cells exhibited a ten-fold higher ROS production compared to Raji. Neither differential incorporation, nor efflux of plumbagin was detected. Pre-treatment with thiol-containing antioxidants prevented ROS production and subsequent induction of cell death by apoptosis whereas non-thiol-containing antioxidants remained ineffective in both cellular models. We conclude that the anticancer potential of plumbagin is driven by pro-oxidant activities related to the cellular thiolstat.
Highlights
Development of anti-cancer drug resistance and differential susceptibility of patients remain the main factors reducing the effectiveness of current chemotherapeutic treatments
Our findings indicate an ability of plumbagin to eventually lead to the modulation of important intracellular functions especially those dominated by thiol modulation, which include enzymes controlling and/or modulating the cellular redox status in cancer cells
Cells were pre-treated with Buthionine sulfoximine (BSO) and different antioxidants (DTT, NAC, Tiron and Trolox) prior to reactive oxygen species (ROS) analysis by flow cytometry; (B) Mitochondrial membrane potential was determined in U937 cells 24 h after plumbagin treatment; (C) ROS measurement in Raji cells was performed under the same conditions as used for U937 cells (see point (A)); (D) Mitochondrial membrane potential was determined in Raji cells 24 h after plumbagin treatment
Summary
Development of anti-cancer drug resistance and differential susceptibility of patients remain the main factors reducing the effectiveness of current chemotherapeutic treatments. Whether extracted from terrestrial or marine organisms, offer a large variability of molecular scaffolds with anti-cancer potential. They derive from medicinal or dietary traditions that already provided health-promoting effects for centuries [4,5,6,7]. Mechanistic studies suggest that the anti-cancer effects of plumbagin depend mostly on its ubiquitous pro-oxidant activities. Plumbagin was shown to inhibit glutathione-S-transferase (GST) [47,48] These findings suggest that plumbagin regulates the cellular redox state by modulation of GSH even though additional redox-dependent mechanisms could be directly or indirectly involved. We suggest a differential expression of redox-related factors as potential regulators of the observed differential susceptibility
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
