Abstrakt: |
The pharmaceutical potential of lichens and their secondary metabolites has recently attracted increasing attention worldwide. Although chemotherapy is a common treatment for cancer, it has a wide range of serious side effects, including myeloand immunosuppression, hepatotoxicity, and neurotoxicity. Combination therapies using natural substances are widely recommended to attenuate the adverse effects of chemotherapy. The aim of this study was to investigate the antileukemic potential of extract from the lichen Pseudevernia furfuracea (L.) Zopf (PSE) and isolated physodic acid (Phy) in an in vitro acute lymphoblastic leukemia (ALL) model. Our results showed that PSE and Phy treatment induced apoptosis in Jurkat cells in a dose- and time-dependent manner. We confirmed that ROS production and consequent DNA damage played an important role in PSE- and Phy-mediated apoptosis. Moreover, the DNA repair mechanism, including the phosphorylation of ATM, H2A.X, and SMC1 proteins, was subsequently activated, followed by p21, p53, and p27 activation and cell cycle arrest. Moreover, PSE and Phy treatment led to the phosphorylation of MAPK signalling, including p38 MAPK, JNK, and PI3K/Akt. Furthermore, minimal or no cytotoxicity in normal peripheral lymphocytes supports the use of PSE and Phy as antileukemic agents. However, future studies might be needed to determine more associated mechanisms of the anticancer action of the tested substances more deeply. [ABSTRACT FROM AUTHOR] |