BRAF inhibitor candidate molecule usnic acid might use both intrinsic and extrinsic pathways of apoptosis

Sep 21, 2026

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Melanoma is an aggressive cancer, yet effective therapies remain limited due to resistance and toxicity from checkpoint and BRAF/MEK inhibitors, chemotherapy, radiation, and adjuvant approaches. This study assesses the anticancer action of usnic acid (UA) on A-375 melanoma cells and human epidermal melanocytes using real-time xCELLigence analysis. UA increases caspase-3 and caspase-9 activities and modulates 61 proapoptotic genes up and 23 antiapoptotic genes down, suggesting engagement of intrinsic and extrinsic apoptosis pathways.

LanguageEnglish

CategoryHealthcare

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Pages15

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Materials and Methods

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Introduction

Turkish Journal of Medical Sciences Manuscript 5890 BRAF inhibitor candidate molecule usnic acid might use both intrinsic and extrinsic pathways of apoptosis BURCU PELİN BUYUK DEMET CANSARAN DUMAN TURKER DUMAN Follow this and additional works at: [https://journals.tubitak.gov.tr/medical](https://journals.tubitak.gov.tr/medical) Part of the Medical Sciences Commons This work is licensed under a Creative Commons Attribution 4.0 International License. | | Turkish Journal of Medical Sciences [http://journals.tubitak.gov.tr/medical/](http://journals.tubitak.gov.tr/medical/) | Turk J Med Sci (2024) 54: 1116-1126 © TÜBİTAK | | --- | --- | --- | | |
Research Article | doi:10.55730/1300-0144.5890 | BRAF inhibitor candidate molecule usnic acid might use both intrinsic and extrinsic pathways of apoptosis Burcu Pelin BÜYÜK1􀁋, Demet CANSARAN DUMAN2􀁋, Türker DUMAN1,3,*􀁋 1 Department of Biology, Faculty of Science, Ankara University, Ankara, Turkiye 2 Biotechnology Institute, Ankara University, Ankara, Turkiye 3 Rare Diseases Application and Research Center, Ankara University, Ankara, Turkiye Received: 25.06.2024 Accepted/Published Online: 09.08.2024 Final Version: 18.10.2024 Background/aim: Melanoma is one of the most aggressive cancers and treatment methods commonly used for patients with skin cancer include checkpoint and BRAF/MEK inhibitors, traditional chemotherapy drugs, radiation, and adjuvant treatment methods. Due to the resistance and toxic effects that patients develop against the drugs, an effective treatment method has not been developed for melanoma yet. In this study we evaluated the anticancer effect of usnic acid (UA) on A-375 melanoma cells and human epidermal melanocytes using the xCELLigence real-time cell analysis system. Materials and methods: To determine the cell death pathway through which UA exerts its antiproliferative effect, its potential forapoptotic effects was investigated. Caspase-3 and caspase-9 enzyme assays and the expression analysis of 84 genes from the apoptosis pathway were carried out in UA-treated and nontreated A-375 cells. Results: UA was found to have an antiproliferative effect on A-375 cells while it did not have a cytotoxic effect on human epidermal melanocytes. UA treatment led to statistically significant increases in both caspase-3 and caspase-9 enzyme activities. Moreover, the expression levels of 61 genes (mainly proapoptotic genes) were increased and the expression levels of 23 genes (mainly antiapoptotic genes) were decreased in response to UA treatment. This effect might have developed through both the extrinsic and intrinsic apoptosis pathways; however, the extrinsic pathway was more pronounced. Conclusion: As a result of the obtained findings, it could be concluded that UA might be a promising candidate drug molecule for melanoma treatment in the future through topical application or encapsulation with nanocarriers. Key words: Melanoma, usnic acid, apoptosis, caspases 1. Introduction Usnic acid (UA) is a naturally occurring secondary metabolite of the fungal partner of lichen. It is known for its (+)-UA and (-)-UA enantiomers, which are distinguished by the orientation of the methyl group at position 9b [1] . Its dibenzofuran structure is what distinguishes UA, also known by the chemical name 2,6-diacetyl-7,9-dihydroxy- 8,9b-dimethyl-1,3(2H,9bH)-dibenzofurandione. A major target for the pharmaceutical industry, UA possesses a variety of biological activities including antimicrobial, antiviral, antiprotozoal, antiproliferative, anticancer, antiinflammatory, antimetastatic, antiangiogenic, and analgesic activity [2] . Moreover, UA has been used as a component of various commercial products including mouthwashes, sunscreens, lotions, toothpastes, and deodorants [3]. The first study highlighting the anticancer potential of UA was conducted by Kupchanand Kopperman [4], who determined the effects of UA extracted from * [Correspondence

FAQs

What was the main objective of the study on usnic acid (UA)?

To evaluate the anticancer effect of UA on melanoma cells and to determine which apoptosis cell-death pathway mediates its antiproliferative action.

How were apoptosis-related effects measured in UA-treated A-375 cells?

Caspase-3 and caspase-9 enzyme assays were performed, and expression analysis of 84 apoptosis-pathway genes was conducted in UA-treated versus untreated cells.

What did UA do in terms of gene expression and apoptosis pathway involvement?

UA increased expression of 61 mainly proapoptotic genes and decreased expression of 23 mainly antiapoptotic genes. The apoptotic response suggested both intrinsic and extrinsic pathways, with the extrinsic pathway more pronounced.

Sep 21, 2026

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