Organoselenium Compounds as Novel Adjuvants of Chemotherapy Drugs—A Promising Approach to Fight Cancer Drug Resistance

Abstract

Malignant diseases present a serious public health burden and their treatment with traditional chemotherapy cannot be considered an all-round solution, due to toxic side effects. Selenium compounds (Se-compounds) have received substantial attention in medicinal chemistry, especially in experimental chemotherapy, both as cytotoxic agents and adjuvants in chemotherapy. A checkerboard microplate method was applied to study the drug interactions of Se-compounds and clinically relevant chemotherapeutic drugs against the multidrug-resistant (MDR) subtype of mouse t-lymphoma cells overexpressing the ABCB1 transporter. Se-compounds showed synergistic interactions with chemotherapeutic agents targeting the topoisomerase enzymes or the microtubule apparatus. The ketone-containing selenoesters showed synergism at lower concentrations (1.25 µM). Most of the tested compounds interacted antagonistically with alkylating agents and verapamil. A thiophene-containing Se-compound showed synergism with all tested drugs, except cisplatin. While the exact mechanism of drug interactions is yet unknown, the potency of the selenocompounds as efflux pump inhibitors or the potentiation of their efficacy as reactive oxygen species modulators may play a role in their complementary activity against the tested MDR lymphoma cell line.

Current Biomedical Use of Copper Chelation Therapy

“…Therefore, different clinical trials have been performed to evaluate copper chelation therapy as a tool to overcome platinum-based drug resistance in cancer patients [137][138][139] (Table 4). In addition, selenium compounds, used both as cytotoxic agents and as adjuvants in chemotherapy [140], exhibit the ability to chelate copper [141]. Another promising class of metal complexes suitable for anticancer therapy is represented by Cu(II) chelate complexes [142].…”

Inhibition–Disruption of Candida glabrata Biofilms: Symmetrical Selenoesters as Potential Anti-Biofilm Agents

“…At this stage, the underlying mechanism of action of these novel selenoesters against C. glabrata is unknown and more experiments are needed to determine the ultimate mechanism behind the antifungal activity described herein. Selenocompounds and among them, selenoesters, as briefly mentioned in the introduction [31][32][33][34][35][36][37][38][39], have been proven in previous works to be able to exert a wide range of interesting biological activities, both in the anticancer and The effect of Se-8 on the formation of biofilms generated by C. glabrata dental isolates at t = 0 or 24 h and 4 µg/mL was very weak (0.15 ± 0.03-0.80 ± 0.08 BBU, and 0.07 ± 0.03-0.51 ± 0.14 BBU, respectively), compared to caspofungin (0.93 BBU ± 0.03, 0.56 ± 0.17 BBU, respectively), being statistically significant, p < 0.0001. Selenocompound had the lowest biofilm-reducing effect at 0 and 24 h among the four selenocompounds evaluated in this anti-biofilm assay.…”

“…At this stage, the underlying mechanism of action of these novel selenoesters against C. glabrata is unknown and more experiments are needed to determine the ultimate mechanism behind the antifungal activity described herein. Selenocompounds and among them, selenoesters, as briefly mentioned in the introduction [31][32][33][34][35][36][37][38][39], have been proven in previous works to be able to exert a wide range of interesting biological activities, both in the anticancer and antimicrobial fields; for example, the modulation of the redox cellular state, scavenging of free radicals, increase of the oxidative stress, induction of apoptosis, and inhibition of efflux pumps, among others [31][32][33][34][35][36][37][38][39]. With the caveat that future works would need to prove it, we could hypothesize that one of several of these mechanisms could explain the observed activities for the symmetrical selenoesters presented in this work.…”

“…Regarding selenium, certain selenium derivatives or selenium nanoparticles have shown antifungal activity [28][29][30]. In this context, our group has reported in previous works the activity of selenoesters and selenoanhydrides against cancer cells [31], cancer multi-drug resistance [32], and resistant bacteria as Staphylococcus aureus and Chlamydia trachomatis [33], among other biological effects. The mechanisms of action of the selenocompounds are very diverse [34].…”

Bioactivity and DNA/BSA Interactions of Selenium N‐Heterocyclic Carbene Adducts

“…Therefore, Organo-selenium (org-se) compounds are getting substantial attention due to their pronounced biological activities [15] and a number of research reports highlighting the antioxidant, antiinflammatory, anti-neurodegenerative and antimicrobial activity of org-Se compounds. [16,17] For example, Ebselen and its derivatives showed excellent potential against resistant bacterial strains MRSA, VRSA and M. Tuberculosis. [18] The other selenides and selenones were also studied for their antibiotic spectrum and found very active with very lower MIC values against both broader spectrum of bacterial strains (grampositive and gram-negative).…”