The Influence of Antitumor Unsymmetrical Bisacridines on 3D Cancer Spheroids Growth and Viability.

Jolanta Kulesza,Monika Pawłowska,Ewa Augustin

doi:10.3390/molecules26206262

Jolanta Kulesza, Monika Pawłowska + Show 1 more

Open Access

https://doi.org/10.3390/molecules26206262

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Abstract

The culture of 3D spheroids is a promising tool in drug development and testing. Recently, we synthesized a new group of compounds, unsymmetrical bisacridines (UAs), which exhibit high cytotoxicity against various human cell lines and antitumor potency against several xenografts. Here, we describe the ability of four UAs—C-2028, C-2041, C-2045, and C-2053—to influence the growth of HCT116 and H460 spheres and the viability of HCT116 cells in 3D culture compared with that in 2D standard monolayer culture. Spheroids were generated using ultra-low-attachment plates. The morphology and diameters of the obtained spheroids and those treated with UAs were observed and measured under the microscope. The viability of cells exposed to UAs at different concentrations and for different incubation times in 2D and 3D cultures was assessed using 7-AAD staining. All UAs managed to significantly inhibit the growth of HCT116 and H460 spheroids. C-2045 and C-2053 caused the death of the largest population of HCT116 spheroid cells. Although C-2041 seemed to be the most effective in the 2D monolayer experiments, in 3D conditions, it turned out to be the weakest compound. The 3D spheroid culture seems to be a suitable method to examine the efficiency of new antitumor compounds, such as unsymmetrical bisacridines.

Highlights

For many years, cancer has been the second leading cause of death in the world [1].a big challenge for modern medicine is the development of new, effective anticancer drugs, which, is a difficult task and involves a lot of costly and time-consuming research
unsymmetrical bisacridines (UAs) inhibited the proliferation of both HCT116 and H460 cells at low Molecules 2021, 26, 6262 concentrations, and the effects were similar for both cancer cell lines
In this study we focused on the influence of four newly synthesized antitumor compounds, unsymmetrical bisacridines (UAs), on the growth and viability of spheroids derived from colon HCT116 and lung H460 cells

Summary

Introduction

Cancer has been the second leading cause of death in the world [1].a big challenge for modern medicine is the development of new, effective anticancer drugs, which, is a difficult task and involves a lot of costly and time-consuming research. Spheroids consist of different proliferation areas that are defined due to the nutrients, metabolites, pH, and oxygen gradients These features, along with different gene expression patterns than in a monolayer culture, are similar to those found in poorly vascularized or avascular solid tumors [6,7,8]. This makes 3D spheroid cell culture systems useful models for the study of cancer biology, including anticancer drug testing. Spheroids are a good tool for the selection of chemotherapeutic agents with increased distribution and effectiveness in environments similar to in vivo conditions and may help

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