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c-Myc Protein Level Affected by Unsymmetrical Bisacridines Influences Apoptosis and Senescence Induced in HCT116 Colorectal and H460 Lung Cancer Cells
Abstract
Unsymmetrical bisacridines (UAs) are highly active antitumor compounds. They contain in their structure the drugs previously synthesized in our Department: C-1311 and C-1748. UAs exhibit different properties than their monomer components. They do not intercalate to dsDNA but stabilize the G-quadruplex structures, particularly those of the MYC and KRAS genes. Since MYC and KRAS are often mutated and constitutively expressed in cancer cells, they can be used as therapeutic targets. Herein, we investigate whether UAs can affect the expression and protein level of c-Myc and K-Ras in HCT116 and H460 cancer cells, and if so, what are the consequences for the UAs-induced cellular response. UAs did not affect K-Ras, but they strongly influenced the expression and translation of the c-Myc protein, and in H460 cells, they caused its full inhibition. UAs treatment resulted in apoptosis, as confirmed by the morphological changes, the presence of sub-G1 population and active caspase-3, cleaved PARP, annexin-V/PI staining and a decrease in mitochondrial potential. Importantly, apoptosis was induced earlier and to a greater extent in H460 compared to HCT116 cells. Moreover, accelerated senescence occurred only in H460 cells. In conclusion, the strong inhibition of c-Myc by UAs in H460 cells may participate in the final cellular response (apoptosis, senescence).
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- DOI:
- Digital Object Identifier (open in new tab) 10.3390/ijms23063061
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- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
no. 23,
ISSN: 1661-6596 - Language:
- English
- Publication year:
- 2022
- Bibliographic description:
- Pawłowska M., Kulesza J., Augustin E.: c-Myc Protein Level Affected by Unsymmetrical Bisacridines Influences Apoptosis and Senescence Induced in HCT116 Colorectal and H460 Lung Cancer Cells// INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES -Vol. 23,iss. 6 (2022), s.3061-
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/ijms23063061
- Sources of funding:
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- Project Biological response induced by high antitumor active unsymmetrical bisacridines against human colon and lung cancers and improved by nanoparticles drug delivery.
- 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.
- Verified by:
- Gdańsk University of Technology
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