Research Article
Year 2023,
Volume: 82 Issue: 2, 251 - 257, 21.12.2023
Abstract
Objective: Nuclear factor kappa B (NF-κB) is one pathway that controls the expression of genes involved in many cancer events such as proliferation, apoptosis, metastasis, and invasion. Usnic acid is a molecule with many biological effects such as being anticholinergic, gastroprotective, anti-inflammatory, anti-cancerous, and especially antioxidant. This study aims to mechanistically examine the apoptotic behaviors of usnic acid in DU145 prostate cancer cells and the molecules it acts on in the NF-κB pathway.
Materials and Methods: This study investigates the apoptotic changes in DU145 cells after usnic acid administration through JC-1 staining and caspase-3 activity measurements. In addition, it tests the effects of usnic acid on subunit p50 and p65 protein and gene expressions in the NF-κB pathway through the respective Western blot and qPCR measurements.
Results: The IC50 values of usnic acid at 24 and 48 h in DU145 cells were calculated as 167.06±12.35 μM and 42.15±3.76 μM, respectively. In addition, JC-1 staining showed usnic acid-treated DU145 cells to trigger apoptosis by increasing the membrane permeability of their mitochondria. NF-κB p50 protein expression was also found to be suppressed after usnic acid administration.
Conclusion: The results of this study show usnic acid administration to suppress proliferation and to induce mitochondrial apoptosis by suppressing the NF-κB pathway in DU145 cells. This effect of usnic acid indicates it to be combinable with chemotherapeutic agents and evaluable as an alternative in cancer treatment.
Keywords
References
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Year 2023,
Volume: 82 Issue: 2, 251 - 257, 21.12.2023
Abstract
References
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- Rawla P. Epidemiology of prostate cancer. World J Oncol. 2019;10(2):63-89. google scholar
- Hurwitz M. Chemotherapy in prostate cancer. Curr Oncol Rep. 2015;17:1-10. google scholar
- Erstad DJ, Cusack JC. Targeting the NF-kB pathway in cancer therapy. Surg Oncol Clin. 2013;22(4):705-746. google scholar
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- Pramyothin P, Janthasoot W, Pongnimitprasert N, Phrukudom S, Ruangrungsi N. Hepatotoxic effect of (+) usnic acid from Usnea siamensis Wainio in rats, isolated rat hepatocytes and isolated rat liver mitochondria. J Ethnopharmacol. 2004;90(2-3): 381-387. google scholar
- Sonko BJ, Schmitt TC, Guo L, et al. Assessment of usnic acid toxicity in rat primary hepatocytes using 13C isotopomer dis-tribution analysis of lactate, glutamate and glucose. Food Chem Toxicol. 2011;49(11):2968-2974. google scholar
- Sahu SC, Amankwa-Sakyi M, O’Donnell Jr MW, Sprando RL. Effects of usnic acid exposure on human hepatoblastoma HepG2 cells in culture. J Appl Toxicol. 2012;32(9):722-730. google scholar
- Mariappan N, Elks CM, Sriramula S, et al. NF-kB-induced oxida-tive stress contributes to mitochondrial and cardiac dysfunction in type II diabetes. Cardiovasc Res. 2010;85(3):473-483. google scholar
- Elks CM, Mariappan N, Haque M, Guggilam A, Majid DS, Fran-cis J. Chronic NF-kB blockade reduces cytosolic and mitochon-drial oxidative stress and attenuates renal injury and hypertension in SHR. Am J Physiol Renal Physiol. 2009;296(2):298-305. google scholar
- Takai M, Uehara Y, Beisler JA. Usnic acid derivatives as potential antineoplastic agents. JMed Chem. 1979; 22(11):1380-1384. google scholar
- Cardarelli M, Serino G, Campanella L, et al. Antimitotic effects of usnic acid on different biological systems. Cell Mol Life Sci. 1997;53:667-672. google scholar
- Backorova M, Jendzelovsky R, Kello M, Backor M, Mikes J, Fedorocko P. Lichen secondary metabolites are responsible for induction of apoptosis in HT-29 and A2780 human cancer cell lines. Toxicol In Vitro. 2012;26(3): 462-468. google scholar
- Dincsoy AB, Duman DC. Changes in apoptosis-related gene ex-pression profiles in cancer cell lines exposed to usnic acid lichen secondary metabolite. Turk J Biol. 2017;41(3): 484-493. google scholar
- Jin JQ, Li CQ, He LC. Down-regulatory effect of usnic acid on nu-clear factor-KB-dependent tumor necrosis factor-a and inducible nitric oxide synthase expression in lipopolysaccharide-stimulated macrophages RAW 264.7. Phytother Res. 2008; 22(12):1605-1609. google scholar
There are 34 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Plant Cell and Molecular Biology, Animal Cell and Molecular Biology |
| Journal Section | Themed Articles - Research Articles |
| Authors | |
| Publication Date | December 21, 2023 |
| Submission Date | March 31, 2023 |
| Published in Issue | Year 2023 Volume: 82 Issue: 2 |
