Effects of electroporation on anticancer activity of 5-FU and newly synthesized zinc(II) complex in chemotherapy-resistance human brain tumor cells

Abstract

Zn(II) complex of Schiff base derived from the condensation of 4-aminopyrimidine-2(1H)-one with salicylaldehyde was prepared and characterized by various physico-chemical and spectral methods for structure determination. The cytotoxic activity of the Zn(II) complex was investigated in comparison with 5-uorouracil (5-FU) against two different human brain tumor cell lines (T98G and U118), while primer human dermal broblast cells (HDF) was used as control for biocompatibility. Then, the effectiveness of electroporation (EP) on cytotoxic activities of these compounds has been examined. The cytotoxicities of the 5-FU and new Zn(II) complex, alone or in combination with electroporation, were determined by MTT assay. The Zn(II) complex showed good cytotoxicity against T98G and U118 brain tumor cell lines with IC 50 = 282.47 and 297.91 μM respectively, while it was safe on HDF healthy cells with IC 50 = 826.72 μM.The 5-FU exhibited less cytotoxicity compared to the Zn(II) complex against T98G (IC 50 = 382.35 μM) and U118 (IC 50 = 396.56 μM) tumor cell lines. The combined application of Zn (II) + EP decreased the IC 50 value by 5.96-fold in T98G cells and 4.76-fold in U118 cells. EP showed a similar effect in its combined application with 5-FU, resulting in a decrease of the IC 50 value of 4.22-fold in the T98G cells and 3.84-fold in the U118 cells. In a conclusion, the Zn(II) complex exhibited an anticancer potential against both brain tumor cell lines (T98G and U118) and EP greatly increased the cytotoxicity of Zn(II) complex and 5-FU on these chemotherapy-resistant cells. HighlightsNovel Zn(II) complex were synthesized and characterized by various physico-chemical and spectral methods.The cytotoxic activity of the Zn(II) complex was investigated in comparison with 5-Fu against T98G, U118 and broblast (HDF) cell lines.Electroporation greatly enhanced the anticancer effect of Zn(II) complex and 5-Fu in brain chemotherapy-resistant cells.The application of the new Zn(II) complex alone or in combination with electroporation showed higher cytotoxicity than 5-Fu in the treatment of T98G and U118 brain tumor cell lines.

Padina boergesenii mediated synthesis of Se-ZnO bimetallic nanoparticles for effective anticancer activity

“…A study by Yang et al (2022) stated that the Selenium in combination with doxorubicin has high attenuation of cancer cells. Similarly, the combination of Zinc and 5-FU complexes showed anti-cancer activity against brain tumor cells and breast tumor cells ( Hu et al, 2012 ; Alkış et al, 2021 ). As mentioned in the study of Saranya et al (2022) , It has been found that the combination of apigenin with Se NPs significantly increases MDA (malondialdehyde) production in cancer cells, suggesting it is a potential therapeutic approach in the fight against breast cancer.…”

Elektroporasyon İşlemi Sırasında Oluşan Hücre Ölümünde Darbe Frekansının Önemi

“…ECT'de uygulanacak darbe parametreleri hücre içine antikanser ajan geçişini kolaylaştırırken, minimum düzeyde hücre ölümüne neden olmalıdır. Daha önce yapılan in vitro ECT çalışmalarında tek başına uygulanan elektroporasyonun, değişik oranlarda hücre ölümüne neden olabildiği bildirilmiştir [8,26,27,28,29]. Uygulanan elektrik darbelerinin tipi, sayısı, süresi, frekansı ve genliği gibi parametreler hücre geçirgenliğini, ölümünü ve altyapısını değiştirebilmektedir [30].…”