期刊
PHARMACEUTICS
卷 13, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/pharmaceutics13122173
关键词
acute lymphoblastic leukemia; Pseudevernia furfuracea; physodic acid; apoptosis; oxidative stress; DNA damage; cell cycle checkpoints; MAPK
资金
- Grant Agency of the Ministry of the Education, Science, Research and Sport of the Slovak Republic [VEGA 1/0753/17, 1/0653/19, 1/0539/21, KEGA 006UPJS-4/2020]
- Slovak Research and Development Agency [APVV-16-0446]
- Operational Programme Integrated Infrastructure - ERDF [ITMS2014+: 313011V455]
The study investigated the anti-leukemic potential of lichen extract and physodic acid in ALL treatment, demonstrating their ability to induce cell death while causing minimal toxicity in normal cells.
Acute lymphoblastic leukemia (ALL) is the most frequently diagnosed type of leukemia among children. Although chemotherapy is a common treatment for cancer, it has a wide range of serious side effects, including myelo- and immunosuppression, hepatotoxicity and neurotoxicity. Combination therapies using natural substances are widely recommended to attenuate the adverse effects of chemotherapy. The aim of the present study was to investigate the anti-leukemic potential of extract from the lichen Pseudevernia furfuracea (L.) Zopf (PSE) and isolated physodic acid (Phy) in an in vitro ALL model. A screening assay, flow cytometry and Western blotting were used to analyze apoptosis occurrence, oxidative stress, DNA damage and stress/survival/apoptotic pathway modulation induced by the tested substances in Jurkat cells. We demonstrate for the first time that PSE and Phy treatment-induced intrinsic caspase-dependent cell death was associated with increased oxidative stress, DNA damage and cell cycle arrest with the activation of cell cycle checkpoint proteins p53, p21 and p27 and stress/survival kinases p38 MAPK, JNK and PI3K/Akt. Moreover, using peripheral T lymphocytes, we confirmed that PSE and Phy treatment caused minimal cytotoxicity in normal cells, and therefore, these naturally occurring lichen secondary metabolites could be promising substances for ALL therapy.
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