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3D spheroid culture system of HCT116 colon and A549 lung cancer cells in the study of the cellular response induced by antitumor unsymmetrical bisacridines in these cells.
Abstract
3D spheroid culture is a promising tool in cancer research, especially in drug development and testing. Here, the effects of antitumor unsymmetrical bisacridines (UAs) on 3D spheroids of HCT116 colon and A549 lung cancer cells were studied. The influence of four UAs: C-2028, C-2041, C-2045 and C-2053 on the morphology, size and viability of A549 cells was tested and compared with the results obtained for HCT116 cells [Kulesza J. et al. (2021) Molecules 26, 6262]. Furthermore, the spherogenicity of HCT116 and A549 cells after UAs treatment was evaluated, together with the ability of the cells to return to proliferation following UAs exposure. We showed that UAs treatment of A549 spheroids resulted in a gradual reduction of their size in the case of three tested compounds (C-2028, C-2045, C-2053) and after 14 days the spheroids were almost 20% smaller than on day 0. C-2041 and etoposide, did not cause the reduction of spheres below baseline sizes. Cell viability evaluated using the 7-AAD dye revealed that both HCT116- and A549- cultures showed a significant amount of non-viable cells after treatment with UAs and this fraction was generally higher in 2D than in 3D. Moreover, 14 days after exposure to C-2041, C-2045 and etoposide, 100% of A549 cells were able to form spheroids, while C-2028 and C-2053 completely inhibited the spherogenicity of these cells. In HCT116 cells, some degree of spherogenic potential was visible after incubation with all UAs and irinotecan, but 100% of spheres were formed only after C-2041 treatment. The colony formation assay showed that 72h exposure of A549 and HCT116 cells to UAs (except C-2041) resulted in a complete inhibition of their proliferation. Obtained results showed the importance of testing potential antitumor drugs in both 2D and 3D environments and proved that UAs exhibit anticancer properties in both culture models. Studies supported by the National Science Center, Poland, Grants No. 2016/23/B/NZ7/03324 and 2019/33/B/NZ7/02534.
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- Category:
- Articles
- Type:
- suplement w czasopiśmie
- Published in:
-
FEBS Open Bio
no. 12,
ISSN: 2211-5463 - Language:
- English
- Publication year:
- 2022
- DOI:
- Digital Object Identifier (open in new tab) 10.1002/2211-5463.13441
- Sources of funding:
-
- Project Specific interactions of new antitumor unsymmetrical bisacridines, UAs, with DNA and ABC proteins and their potential to modulate the enzymatic activity and trancription of nuclear receptor as the elements of their molecular mechanism of action.
- Project Biological response induced by high antitumor active unsymmetrical bisacridines against human colon and lung cancers and improved by nanoparticles drug delivery.
- Verified by:
- Gdańsk University of Technology
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