Pro-Apoptotic Potential of Pseudevernia furfuracea (L.) Zopf Extract and Isolated Physodic Acid in Acute Lymphoblastic Leukemia Model In Vitro

Abstract

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.

Phenolic Secondary Metabolites and Antiradical and Antibacterial Activities of Different Extracts of Usnea barbata (L.) Weber ex F.H.Wigg from Călimani Mountains, Romania

“…These constituents are deposited as crystals on fungal hyphae in the cortex or medulla; the different distribution in the thallus layers is correlated with their biological actions [ 3 ]. The lichen’s most significant pharmacological activities are antioxidant [ 4 ], antimicrobial [ 5 ], anticancer [ 6 ], photoprotective [ 7 ], and anti-inflammatory [ 8 ]. Therefore, they are considered important representatives with biopharmaceutical potential [ 9 ].…”

Lichen Secondary Metabolites Inhibit the Wnt/β-Catenin Pathway in Glioblastoma Cells and Improve the Anticancer Effects of Temozolomide

“…Similar results were also obtained by Cardile et al, who found that physodic acid activated an apoptotic process, probably involving the reduction of Hsp70 expression, in A375 melanoma cancer cells [ 33 ]. In another study, the treatment of Jurkat cells with an extract from the lichen Pseudevernia furfuracea and its major constituent, physodic acid, resulted in intrinsic caspase-dependent cell death induction, which was associated with increased oxidative stress, DNA damage, and cell cycle arrest [ 38 ]. The authors report the activation of cell cycle checkpoint proteins p53, p21, and p27 and stress/survival kinases p38 MAPK, JNK, and PI3K/Akt as a result of P. furfuracea and physodic acid treatment [ 38 ].…”

“…In another study, the treatment of Jurkat cells with an extract from the lichen Pseudevernia furfuracea and its major constituent, physodic acid, resulted in intrinsic caspase-dependent cell death induction, which was associated with increased oxidative stress, DNA damage, and cell cycle arrest [ 38 ]. The authors report the activation of cell cycle checkpoint proteins p53, p21, and p27 and stress/survival kinases p38 MAPK, JNK, and PI3K/Akt as a result of P. furfuracea and physodic acid treatment [ 38 ]. In our study, squamatic acid, salazinic acid, and lecanoric acid also induced apoptosis in GBM cells, and the percentage of apoptotic cells was even higher as compared to the effects of the 100 nM anticancer drug, topotecan.…”

Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications

“…Probably plants are the most well-known source of molecules with demonstrated anticancer therapeutic properties. Another set of papers of this Special Issue have investigated the antitumoral properties of plant extracts and plant-derived compounds, revealing interesting antiproliferative and/or pro-apoptotic activities in vitro [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. In addition, Huang and coworkers have shown that Ceylon olive leaf extract and its phytochemicals, such as mearnsetin, displayed potent antimelanogenesis effects in a zebrafish model [ 19 ].…”

“…Increasing evidence indicates that compounds derived from some plants have a role in neuroprotection. Two articles of this Special Issue focused on the utilization of plant-derived compounds as neuroprotective [ 24 ] or neuromodulatory [ 15 ] agents. In the first of such studies, Meganova and coworkers evaluated the effects of novel hydroxamic acid derivatives in a 5xFAD transgenic mice model of Alzheimer’s disease (AD).…”