Evaluation of the cytostatic properties of berberine derivatives on a cell culture of acute T-cell lymphoblastic leukemia (Jurkat).

Abstract

e19114 Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that accounts for 25% of all adult cases of T-ALL. Currently, the frequency of disease recurrence and resistance to therapy remains quite high, so there is an urgent need to improve therapy by testing new compounds that may potentially have antitumor activity. Promising compounds include berberine, whose high antitumor activity we previously confirmed on glioblastomas, and its derivatives. The aim of the study was to evaluate the cytotoxic effect of berberine derivatives on Jurkat cell culture in an in vitro experiment. Methods: Jurkat cell culture cells were cultured in a complete RPMI1640 nutrient medium without phenolic red (Gibco, USA) with the addition of 10% FBS (Hyclone, USA), 1% glutamine (Biolot, Russia). A total of 11 compounds were tested: berberine and its derivatives ZbRNN, Rub, NAPh, Rub HCl, 12NO2, EPOX, Mag-2, Mag-1, AkR(1) Fuz, 21A. Dose-response curves were constructed for each compound, measuring the level of metabolically active cells by colorimetric method using tetrazolium salt XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide). The exposure time was 72 hours. Viability was determined as the ratio of the number of living cells in the experimental wells to the control wells, expressed as a percentage. Based on the data obtained, dose-response curves were constructed and IC50 values were determined using the dcr package of the R programming language. Results: Compounds MAG-1, MAG-2, 21A, ZbRNN, Rub, 12NO2, EPOX, and NAPh demonstrated high activity (IC50 below 1000 nmol/L) against the Jurkat cell line. The IC50 value for the studied substances was: 236.4±33.5 nmol/L, 31.8±9.1 nmol/L, 126.3±27.2 nmol/L, 103.8±13.3 nmol/L, 136.4±18.7 nmol/L, 308.4±39.3 nmol/L, 455.7±54.1 nmol/L and 789.5±26.6 nmol/l, respectively (p<0.05). For compounds Rub HCl and AkR(1) Fuz, the IC50 value exceeded 1000 nmol/l and amounted to 1756.2±99.1 nmol/l and 1435.7±112.8 nmol/L (p<0.05). For berberine, the IC50 value was 447.6±46.1 nmol/L. Conclusions: The results obtained indicate the pronounced cytostatic properties of a number of berberine derivatives, of particular interest are compounds that are close to and superior to berberine in cytostatic properties.