Please use this identifier to cite or link to this item:
http://dx.doi.org/10.25673/110441
Title: | SESN2 knockdown increases betulinic acid-induced radiosensitivity of hypoxic breast cancer cells |
Author(s): | Güttler, Antje Weinholdt, Claus Ruffert, Elisabeth ![]() Reidt, Judith Darnstaedt, Elisa Wildemann, Alicia Petrenko, Marina Keßler, Jacqueline Kappler, Mathias Große, Ivo ![]() Vordermark, Dirk ![]() Bache, Mathias |
Issue Date: | 2023 |
Type: | Article |
Language: | English |
Abstract: | Betulinic acid (BA) is a natural compound well known for its anti-inflammatory, anti-viral, anti-bacterial, anti-malarial effects and anti-tumor properties. Its enhanced cytotoxicity in tumor cells and induction of cell death in various cancer entities qualifies BA as an interesting candidate for novel treatment concepts. Our analyses showed enhanced cytotoxicity and radiosensitization under hypoxic conditions in human breast cancer cells. So far, the underlying mechanisms are unknown. Therefore, we investigated the BA-treated human breast cancer cell lines MDA-MB-231 and MCF-7 under normoxic and hypoxic conditions based on microarray technology. Hypoxia and BA regulated a variety of genes in both breast cancer cell lines. KEGG pathway analysis identified an enrichment of the p53 pathway in MCF-7 cells (wtp53) under hypoxia. In MDA-MB-231 cells (mtp53) an additional BA incubation was required to activate the p53 signaling pathway. Fourteen down-regulated and up-regulated genes of the p53 pathway were selected for further validation via qRT-PCR in a panel of five breast cancer cell lines. The stress-induced gene Sestrin-2 (SESN2) was identified as one of the most strongly up-regulated genes after BA treatment. Knockdown of SESN2 enhanced BA-induced ROS production, DNA damage, radiosensitivity and reduced autophagy in breast cancer cells. Our results identified SESN2 as an important target to enhance the radiobiological and anti-tumor effects of BA on breast cancer cells. |
URI: | https://opendata.uni-halle.de//handle/1981185920/112396 http://dx.doi.org/10.25673/110441 |
Open Access: | ![]() |
License: | ![]() |
Journal Title: | Cells |
Publisher: | MDPI |
Publisher Place: | Basel |
Volume: | 12 |
Issue: | 1 |
Original Publication: | 10.3390/cells12010177 |
Appears in Collections: | Open Access Publikationen der MLU |
Files in This Item:
File | Description | Size | Format | |
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cells-12-00177-v2.pdf | 4.24 MB | Adobe PDF | ![]() View/Open |