Comparative sensitivity of tumor and non-tumor cell lines as a reliable approach for in vitro cytotoxicity screening of lysine-based surfactants with potential pharmaceutical applications

Abstract

Surfactants are used as additives in topical pharmaceuticals and drug delivery systems.The biocompatibility of amino acid-based surfactants makes them highly suitable for use in these fields, but tests are needed to evaluate their potential toxicity. Here we addressed the sensitivity of tumor (HeLa, MCF-7) and non-tumor (3T3, 3T6, HaCaT, NCTC 2544) cell lines to the toxic effects of lysine-based surfactants by means of two in vitro endpoints (MTT and NRU). This comparative assay may serve as a new approach for predictive toxicity screening of chemicals prior to pharmaceutical applications. After 24-h of cell exposure to surfactants, differing toxic responses were observed. NCTC 2544 and 3T6 cell lines were the most sensitive, while both tumor cells and 3T3 fibroblasts were more resistant to the cytotoxic effects of surfactants. IC 50 -values revealed that cytotoxicity was detected earlier by MTT assay than by NRU assay, regardless of the compound or cell line. The overall results showed that surfactants with organic counterions were less cytotoxic than those with inorganic counterions. Our findings highlight the relevance of the correct choice and combination of cell lines and bioassays in toxicity studies for a safe and reliable screen of chemicals with potential interest in pharmaceutical industry.

Inclusion of a pH-responsive amino acid-based amphiphile in methotrexate-loaded chitosan nanoparticles as a delivery strategy in cancer therapy

“…The choice of 77KS as a bioactive excipient in the NP formulation was based on our previous studies, which showed its pH-sensitive membrane-disruptive activity, together with improved kinetics in the endosomal pH range and low cytotoxic potential (Nogueira et al 2011a(Nogueira et al , 2011b. 77KS was incorporated into the NPs at a concentration below its CMC, thereby indicating that this surfactant is presented in the formulation in its monomer form.…”

“…We chose the in vitro model systems to perform this study, as they provide a rapid and effective means to assess NPs for a number of toxicological endpoints and mechanism-driven responses. Primarly, we evaluated if the unloaded-CS-NPs have any cytotoxic effect, which can be attributed especially to the presence of surfactant (Nogueira et al 2011b). Fig.…”

Evaluation of cytotoxicity, anti-herpes simplex virus type 1 (HSV-1) and antibacterial activities of Ficus vasta and phytoconstituents

“…Naringenin (5) Luteolin (6) Quercetin (7) Vitexin (R= glucose) (8) Quercetin 3-O-β-glucoside (R=glucose) (9) Rutin (10) (Sardari et al, 2009), some of them from the Moraceae family. It is already reported that the cytotoxicity potential of compounds varies with the type of cell line and the method employed to evaluate it (Nogueira et al 2011), also with the type of substance which is investigated and its time of exposition (Van de Sandt, 1992). The screening of anti-HSV-1 activity of the extract was carried on at the highest non-toxic concentration (119 µg/mL) in Vero cells, because being the viruses intracellular parasites, the death of the cells could lead to a false antiviral effect.…”

Free-radical Scavenging properties and Cytotoxic Activity Evaluation of Latex C-serum from Hevea brasiliensis RRIM 600

“…Specific responses related to the cell line tested are described in the literature with different materials. 31 It is possible to infer that for CCD 1059sk cells derived from skin fibroblasts, latex C-serum was not cytotoxic at the concentrations tested. Although more studies of pre-clinical and clinical toxicity are needed, this results can be an indicative of possible therapeutic application of latex C-serum as a treatment for skin diseases related to reactive species or even preventive skin pharmacological formulations.…”

“…11,12 Nogueira et al (2011) 31 recommend that different cell lines from different origins must be used to screen the toxicological effects of new products with potential biomedical applications. For initial screening of latex C-serum potential toxicity, two human cell lines were chosen: MRC-5, derived from lung fibroblasts, and CCD 1059sk, derived from skin fibroblasts.MRC-5 cell line that were exposed to latex C-serum up to the concentration of 50 µg/mL showed no reduction of the cell viability, when compared to the control group.…”