The Molecular Mechanisms of Vulpinic Acid Induced Programmed Cell Death in Melanoma

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2022 Aug 12

PMID 35960408

Authors

Sevcan Yangin

Demet Cansaran-Duman

Gamze Guney Eskiler

Sumer Aras

Affiliations

Soon will be listed here.

Abstract

Backgrounds: Malignant melanoma is an aggressive skin tumor with a rapidly increasing incidence and there is not yet a successful treatment strategy. Vulpinic acid (VA) is derived from secondary metabolites from lichen species. In the current study, we, for the first time, investigated the anti-cancer effects of VA and the underlying mechanism VA induced programmed cell death in melanoma.

Methods: The anti-cancer effects of VA on melanoma cells were evaluated by the xCELLigence system, flow cytometry, caspase-3 activity and RT-PCR analysis.

Results: Our results showed that VA had a strong anti-proliferative effect on A-375 melanoma cells without damaging human epidermal melanocyte cells. Additionally, VA promoted apoptotic cell death through G2/M arrest and the activation of both intrinsic and extrinsic apoptosis pathways according to the analysis of 88 genes associated with apoptosis by qRT-PCR.

Conclusions: Our findings suggest that VA could become an alternative topical and transdermal treatment strategy in the treatment of maligned melanoma cancer. However, further investigations are needed to assess the underlying molecular mechanism of VA mediated apoptotic cell death in the treatment of melanoma.

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References

ONeill C, Scoggins C . Melanoma. J Surg Oncol. 2019; 120(5):873-881. DOI: 10.1002/jso.25604. View

Lo J, Fisher D . The melanoma revolution: from UV carcinogenesis to a new era in therapeutics. Science. 2014; 346(6212):945-9. PMC: 4701046. DOI: 10.1126/science.1253735. View

Jenkins R, Fisher D . Treatment of Advanced Melanoma in 2020 and Beyond. J Invest Dermatol. 2020; 141(1):23-31. PMC: 7541692. DOI: 10.1016/j.jid.2020.03.943. View

Micali G, Lacarrubba F, Nasca M, Schwartz R . Topical pharmacotherapy for skin cancer: part I. Pharmacology. J Am Acad Dermatol. 2014; 70(6):965.e1-12. DOI: 10.1016/j.jaad.2013.12.045. View

Abbas K, Qadir M, Anwar S . The Role of Melanin in Skin Cancer. Crit Rev Eukaryot Gene Expr. 2019; 29(1):17-24. DOI: 10.1615/CritRevEukaryotGeneExpr.2018024980. View

Gray-Schopfer V, Wellbrock C, Marais R . Melanoma biology and new targeted therapy. Nature. 2007; 445(7130):851-7. DOI: 10.1038/nature05661. View

Hammerova J, Uldrijan S, Taborska E, Slaninova I . Benzo[c]phenanthridine alkaloids exhibit strong anti-proliferative activity in malignant melanoma cells regardless of their p53 status. J Dermatol Sci. 2011; 62(1):22-35. DOI: 10.1016/j.jdermsci.2011.01.006. View

Kwon Y, Cha J, Chiang J, Tran G, Giaever G, Nislow C . A chemogenomic approach to understand the antifungal action of Lichen-derived vulpinic acid. J Appl Microbiol. 2016; 121(6):1580-1591. DOI: 10.1111/jam.13300. View

Shrestha G, Thompson A, Robison R, St Clair L . Letharia vulpina, a vulpinic acid containing lichen, targets cell membrane and cell division processes in methicillin-resistant Staphylococcus aureus. Pharm Biol. 2015; 54(3):413-8. DOI: 10.3109/13880209.2015.1038754. View

10.

Molnar K, Farkas E . Current results on biological activities of lichen secondary metabolites: a review. Z Naturforsch C J Biosci. 2010; 65(3-4):157-73. DOI: 10.1515/znc-2010-3-401. View

11.

Koparal A . Anti-angiogenic and antiproliferative properties of the lichen substances (-)-usnic acid and vulpinic acid. Z Naturforsch C J Biosci. 2015; 70(5-6):159-64. DOI: 10.1515/znc-2014-4178. View

12.

Kilic N, Aras S, Cansaran-Duman D . Determination of Vulpinic Acid Effect on Apoptosis and mRNA Expression Levels in Breast Cancer Cell Lines. Anticancer Agents Med Chem. 2018; 18(14):2032-2041. DOI: 10.2174/1871520618666180903101803. View

13.

Broussard L, Howland A, Ryu S, Song K, Norris D, Armstrong C . Melanoma Cell Death Mechanisms. Chonnam Med J. 2018; 54(3):135-142. PMC: 6165917. DOI: 10.4068/cmj.2018.54.3.135. View

14.

Mattia G, Puglisi R, Ascione B, Malorni W, Care A, Matarrese P . Cell death-based treatments of melanoma:conventional treatments and new therapeutic strategies. Cell Death Dis. 2018; 9(2):112. PMC: 5833861. DOI: 10.1038/s41419-017-0059-7. View

15.

Hussein M, Haemel A, Wood G . Apoptosis and melanoma: molecular mechanisms. J Pathol. 2003; 199(3):275-88. DOI: 10.1002/path.1300. View

16.

Galluzzi L, Vitale I, Aaronson S, Abrams J, Adam D, Agostinis P . Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 2018; 25(3):486-541. PMC: 5864239. DOI: 10.1038/s41418-017-0012-4. View

17.

Varol M, Turk A, Candan M, Tay T, Koparal A . Photoprotective Activity of Vulpinic and Gyrophoric Acids Toward Ultraviolet B-Induced Damage in Human Keratinocytes. Phytother Res. 2015; 30(1):9-15. DOI: 10.1002/ptr.5493. View

18.

Cansaran-Duman D, Eskiler G, Colak B, Sozen Kucukkara E . Vulpinic acid as a natural compound inhibits the proliferation of metastatic prostate cancer cells by inducing apoptosis. Mol Biol Rep. 2021; 48(8):6025-6034. DOI: 10.1007/s11033-021-06605-5. View

19.

Hamsa T, Kuttan G . Harmine activates intrinsic and extrinsic pathways of apoptosis in B16F-10 melanoma. Chin Med. 2011; 6(1):11. PMC: 3076298. DOI: 10.1186/1749-8546-6-11. View

20.

Gonzalez Ramirez M, Salvesen G . A primer on caspase mechanisms. Semin Cell Dev Biol. 2018; 82:79-85. PMC: 6043420. DOI: 10.1016/j.semcdb.2018.01.002. View