Anti-cancer efficacy and mechanisms of usnic acid
Main Article Content
Abstract
Cancer is the second deadly disease after cardiovascular diseases. The presently available therapeutic strategies of cancer are insufficient for the cure and betterment of cancer patients. Herein, we have reviewed the therapeutic potential of a lichenic secondary metabolite, the usnic acid, with special emphasis on its anti-cancer efficacy and associated mechanisms. Usnic acid has various biological activities that have been explored and it is utilized by humans from ancient times throughout the globe. A summary of the anti-cancer properties of usnic acid in different cancer types and models is presented. Usnic acid has shown to inhibit the cancer cell proliferation by suppressing the clonogenic potential, decreasing the expression of PCNA (proliferating cell nuclear antigen), and activating the tumor suppressor genes. Primarily, usnic acid induces reactive oxygen species (ROS) in cancer cells that lead to DNA damage, further causing the activation of DNA damage response that finally initiates the apoptotic pathways. The ROS induction was found to activate the JNK pathway. It also depolarizes the mitochondrial membrane, induces the release of cytochrome-c, and activates the caspase cascade and cleavage of PARP that ultimately results in programmed cell death of cancer cells. Overall, this lichen metabolite has a strong efficacy against cancer cells, which warrants further investigation for its potential clinical uses.
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How to Cite
1.
Kumar K, Mishra J, Singh R. Anti-cancer efficacy and mechanisms of usnic acid. IJPBR [Internet]. 15Jun.2019 [cited 19Apr.2025];7(03):1-. Available from: https://ijpbr.in/index.php/IJPBR/article/view/975
Section
Review Article
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
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4. Huneck, S., et al., The absolute configurations of (+)-usnic and (+)-isousnic acid. X-ray analyses of the (−)-α-phenylethylamine derivative of (+)-usnic acid and of (−)-pseudoplacodiolic acid, a new dibenzofuran, from the lichen Rhizoplaca chrysoleuca. Tetrahedron Letters, 1981. 22(4): p. 351-352.
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8. Vijayakumar, CS, et al., Anti-inflammatory activity of (+)-usnic acid. Fitoterapia, 2000. 71(5): p. 564-6.
9. Su, Z.Q., et al., Usnic acid protects LPS-induced acute lung injury in mice through attenuating inflammatory responses and oxidative stress. Int Immunopharmacol, 2014. 22(2): p. 371-378.
10. Huang, Z., et al., Anti-inflammatory effects and mechanisms of usnic acid. Journal of Wuhan University of Technology-Mater. Sci. Ed., 2011. 26(5): p. 955-959.
11. Bruno, M., et al., (+)-Usnic acid enamines with remarkable cicatrizing properties. Bioorg Med Chem, 2013. 21(7): p. 1834-1843.
12. Nunes, P.S., et al., Collagen-Based Films Containing Liposome-Loaded Usnic Acid as Dressing for Dermal Burn Healing. Journal of Biomedicine and Biotechnology, 2011. 2011: p. 9.
13. Araujo, A.A., et al., Review of the biological properties and toxicity of usnic acid. Nat Prod Res, 2015. 29(23): p. 2167-80.
14. Dos Santos, M.R., et al., Usnic acid-loaded polyaniline/polyurethane foam wound dressing: preparation and bactericidal activity. Mater Sci Eng C Mater Biol Appl, 2018. 89: p. 33-40.
15. Zhang, Z., et al., The effects of sodium usnic acid by topical application on skin wound healing in rats. Biomed Pharmacother, 2018. 97: p. 587-593.
16. Narayanan, D.L., R.N. Saladi, and J.L. Fox, Ultraviolet radiation and skin cancer. Int J Dermatol, 2010. 49(9): p. 978-986.
17. Afaq, F. and H. Mukhtar, Botanical antioxidants in the prevention of photocarcinogenesis and photoaging. Exp Dermatol, 2006. 15(9): p. 678-684.
18. Legouin, B., et al., Specialized Metabolites of the Lichen Vulpicida pinastri Act as Photoprotective Agents. Molecules, 2017. 22(7).
19. Cocchietto, M., et al., A review on usnic acid, an interesting natural compound. Naturwissenschaften, 2002. 89(4): p. 137-46.
20. Lohezic-Le Devehat, F., et al., Lichenic extracts and metabolites as UV filters. J Photochem Photobiol B, 2013. 120: p. 17-28.
21. Lauterwein, M., et al., In vitro activities of the lichen secondary metabolites vulpinic acid, (+)-usnic acid, and (-)-usnic acid against aerobic and anaerobic microorganisms. Antimicrob Agents Chemother, 1995. 39(11): p. 2541-2543.
22. Maciag-Dorszynska, M., G. Wegrzyn, and B. Guzow-Krzeminska, Antibacterial activity of lichen secondary metabolite usnic acid is primarily caused by inhibition of RNA and DNA synthesis. FEMS Microbiol Lett, 2014. 353(1): p. 57-62.
23. Campanella, L., et al., Molecular characterization and action of usnic acid: a drug that inhibits proliferation of mouse polyomavirus in vitro and whose main target is RNA transcription. Biochimie, 2002. 84(4): p. 329-334.
24. Bray, F., et al., Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018. 68(6): p. 394-424.
25. Kupchan, S.M. and HL Kopperman, l-usnic acid: tumor inhibitor isolated from lichens. Experientia, 1975. 31(6): p. 625.
26. Takai, M., Y. Uehara, and J.A. Beisler, Usnic acid derivatives as potential antineoplastic agents. J Med Chem, 1979. 22(11): p. 1380-4.
27. Cardarelli, M., et al., Antimitotic effects of usnic acid on different biological systems. Cell Mol Life Sci, 1997. 53(8): p. 667-72.
28. Mayer, M., et al., Usnic acid: a non-genotoxic compound with anti-cancer properties. Anti-cancer Drugs, 2005. 16(8): p. 805-9.
29. Kumar, K., J.P.N. Mishra, and R.P. Singh, Usnic Acid Inhibits Cell Proliferation Via Downregulation of Proliferating Cell Nuclear Antigen (PCNA) Expression in Gastric Carcinoma AGS Cells. Bioscience biotechnology research communications, 2019. 12(3): p. 609-13.
30. Kumar, K., J.P.N. Mishra, and R.P. Singh, Usnic acid induces apoptosis in human gastric cancer cells through ROS generation and DNA damage and causes up-regulation of DNA-PKcs and γ-H2A.X phosphorylation. Chemico-Biological Interactions, 2020. 315: p. 108898.
31. Singh, N., et al., Usnic acid inhibits growth and induces cell cycle arrest and apoptosis in human lung carcinoma A549 cells. Nutr Cancer, 2013. 65 Suppl 1: p. 36-43.
32. Geng, X., et al., Usnic Acid Induces Cycle Arrest, Apoptosis, and Autophagy in Gastric Cancer Cells In Vitro and In Vivo. Med Sci Monit, 2018. 24: p. 556-566.
33. Yang, Y., et al., Inhibitory Activity of (+)-Usnic Acid against Non-Small Cell Lung Cancer Cell Motility. PLoS ONE, 2016. 11(1): p. e0146575.
34. Durazo, F.A., et al., Fulminant liver failure due to usnic acid for weight loss. Am J Gastroenterol, 2004. 99(5): p. 950-952.
35. Moreira, C.T., et al., Harmful effects of usnic acid on hepatic metabolism. Chem Biol Interact, 2013. 203(2): p. 502-511.
2. Ingolfsdottir, K., Usnic acid. Phytochemistry, 2002. 61(7): p. 729-36.
3. Broksa, B., et al., (-)-Usnic acid and its derivatives. Their inhibition of fungal growth and enzyme activity. Pharmazie, 1996. 51(3): p. 195-6.
4. Huneck, S., et al., The absolute configurations of (+)-usnic and (+)-isousnic acid. X-ray analyses of the (−)-α-phenylethylamine derivative of (+)-usnic acid and of (−)-pseudoplacodiolic acid, a new dibenzofuran, from the lichen Rhizoplaca chrysoleuca. Tetrahedron Letters, 1981. 22(4): p. 351-352.
5. Zuo, S.-t., et al., Usnic acid induces apoptosis via an ROS-dependent mitochondrial pathway in human breast cancer cells in vitro and in vivo. RSC Advances, 2015. 5(1): p. 153-162.
6. Okuyama, E., et al., Usnic acid and diffractaic acid as analgesic and antipyretic components of Usnea diffracta. Planta Med, 1995. 61(2): p. 113-115.
7. Vartia, K.O., Chapter 17 - ANTIBIOTICS IN LICHENS, in The Lichens, V. Ahmadjian and M.E. Hale, Editors. 1973, Academic Press. p. 547-561.
8. Vijayakumar, CS, et al., Anti-inflammatory activity of (+)-usnic acid. Fitoterapia, 2000. 71(5): p. 564-6.
9. Su, Z.Q., et al., Usnic acid protects LPS-induced acute lung injury in mice through attenuating inflammatory responses and oxidative stress. Int Immunopharmacol, 2014. 22(2): p. 371-378.
10. Huang, Z., et al., Anti-inflammatory effects and mechanisms of usnic acid. Journal of Wuhan University of Technology-Mater. Sci. Ed., 2011. 26(5): p. 955-959.
11. Bruno, M., et al., (+)-Usnic acid enamines with remarkable cicatrizing properties. Bioorg Med Chem, 2013. 21(7): p. 1834-1843.
12. Nunes, P.S., et al., Collagen-Based Films Containing Liposome-Loaded Usnic Acid as Dressing for Dermal Burn Healing. Journal of Biomedicine and Biotechnology, 2011. 2011: p. 9.
13. Araujo, A.A., et al., Review of the biological properties and toxicity of usnic acid. Nat Prod Res, 2015. 29(23): p. 2167-80.
14. Dos Santos, M.R., et al., Usnic acid-loaded polyaniline/polyurethane foam wound dressing: preparation and bactericidal activity. Mater Sci Eng C Mater Biol Appl, 2018. 89: p. 33-40.
15. Zhang, Z., et al., The effects of sodium usnic acid by topical application on skin wound healing in rats. Biomed Pharmacother, 2018. 97: p. 587-593.
16. Narayanan, D.L., R.N. Saladi, and J.L. Fox, Ultraviolet radiation and skin cancer. Int J Dermatol, 2010. 49(9): p. 978-986.
17. Afaq, F. and H. Mukhtar, Botanical antioxidants in the prevention of photocarcinogenesis and photoaging. Exp Dermatol, 2006. 15(9): p. 678-684.
18. Legouin, B., et al., Specialized Metabolites of the Lichen Vulpicida pinastri Act as Photoprotective Agents. Molecules, 2017. 22(7).
19. Cocchietto, M., et al., A review on usnic acid, an interesting natural compound. Naturwissenschaften, 2002. 89(4): p. 137-46.
20. Lohezic-Le Devehat, F., et al., Lichenic extracts and metabolites as UV filters. J Photochem Photobiol B, 2013. 120: p. 17-28.
21. Lauterwein, M., et al., In vitro activities of the lichen secondary metabolites vulpinic acid, (+)-usnic acid, and (-)-usnic acid against aerobic and anaerobic microorganisms. Antimicrob Agents Chemother, 1995. 39(11): p. 2541-2543.
22. Maciag-Dorszynska, M., G. Wegrzyn, and B. Guzow-Krzeminska, Antibacterial activity of lichen secondary metabolite usnic acid is primarily caused by inhibition of RNA and DNA synthesis. FEMS Microbiol Lett, 2014. 353(1): p. 57-62.
23. Campanella, L., et al., Molecular characterization and action of usnic acid: a drug that inhibits proliferation of mouse polyomavirus in vitro and whose main target is RNA transcription. Biochimie, 2002. 84(4): p. 329-334.
24. Bray, F., et al., Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018. 68(6): p. 394-424.
25. Kupchan, S.M. and HL Kopperman, l-usnic acid: tumor inhibitor isolated from lichens. Experientia, 1975. 31(6): p. 625.
26. Takai, M., Y. Uehara, and J.A. Beisler, Usnic acid derivatives as potential antineoplastic agents. J Med Chem, 1979. 22(11): p. 1380-4.
27. Cardarelli, M., et al., Antimitotic effects of usnic acid on different biological systems. Cell Mol Life Sci, 1997. 53(8): p. 667-72.
28. Mayer, M., et al., Usnic acid: a non-genotoxic compound with anti-cancer properties. Anti-cancer Drugs, 2005. 16(8): p. 805-9.
29. Kumar, K., J.P.N. Mishra, and R.P. Singh, Usnic Acid Inhibits Cell Proliferation Via Downregulation of Proliferating Cell Nuclear Antigen (PCNA) Expression in Gastric Carcinoma AGS Cells. Bioscience biotechnology research communications, 2019. 12(3): p. 609-13.
30. Kumar, K., J.P.N. Mishra, and R.P. Singh, Usnic acid induces apoptosis in human gastric cancer cells through ROS generation and DNA damage and causes up-regulation of DNA-PKcs and γ-H2A.X phosphorylation. Chemico-Biological Interactions, 2020. 315: p. 108898.
31. Singh, N., et al., Usnic acid inhibits growth and induces cell cycle arrest and apoptosis in human lung carcinoma A549 cells. Nutr Cancer, 2013. 65 Suppl 1: p. 36-43.
32. Geng, X., et al., Usnic Acid Induces Cycle Arrest, Apoptosis, and Autophagy in Gastric Cancer Cells In Vitro and In Vivo. Med Sci Monit, 2018. 24: p. 556-566.
33. Yang, Y., et al., Inhibitory Activity of (+)-Usnic Acid against Non-Small Cell Lung Cancer Cell Motility. PLoS ONE, 2016. 11(1): p. e0146575.
34. Durazo, F.A., et al., Fulminant liver failure due to usnic acid for weight loss. Am J Gastroenterol, 2004. 99(5): p. 950-952.
35. Moreira, C.T., et al., Harmful effects of usnic acid on hepatic metabolism. Chem Biol Interact, 2013. 203(2): p. 502-511.