ArticleBiochemical pharmacology2013
MLK3 is a direct target of biochanin A, which plays a role in solar UV-induced COX-2 expression in human keratinocytes.
Article in Biochemical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- p38 MAPK signaling in chronic obstructive pulmonary disease pathogenesis and inhibitor therapeutics.Cell communication and signaling : CCS · 2023Pooled it
- Biochanin A, a Plant Isoflavone, Disrupts Peptidoglycan Biosynthesis by DownregulatingAntibiotics (Basel, Switzerland) · 2026Article
- Natural Compounds in Non-Melanoma Skin Cancer: Prevention and Treatment.Molecules (Basel, Switzerland) · 2024Review
- Kushenol C fromHeliyon · 2023Article
- Electrospun Poly(lactide) Fibers as Carriers for Controlled Release of Biochanin A.Pharmaceutics · 2022Article
- Perspectives Regarding the Role of Biochanin A in Humans.Frontiers in pharmacology · 2019Review
- Inhibitory Effect ofInternational journal of molecular sciences · 2018Article
- Antiskin Inflammatory Activity of Black GingerOxidative medicine and cellular longevity · 2018Article
- A Combination of Soybean and Haematococcus Extract Alleviates Ultraviolet B-Induced Photoaging.International journal of molecular sciences · 2017Article
- Silkworm Thorn Stem Extract Targets RSK2 and Suppresses Solar UV-Induced Cyclooxygenase-2 Expression.International journal of molecular sciences · 2015Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Solar UV (sUV) is an important environmental carcinogen. Recent studies have shown that sUV is associated with numerous human skin disorders, such as wrinkle formation and inflammation. In this study, we found that the isoflavone, biochanin A, inhibited the expression of sUV-induced COX-2, which is a well-characterized sUV-induced enzyme, in both human HaCaT keratinocytes and JB6 P+ mouse skin epidermal cells. Several studies have demonstrated the beneficial effects of biochanin A. However, its direct molecular target is unknown. We found that biochanin A inhibited sUV-induced phosphorylation of MKK4/JNK/c-Jun and MKK3/6/p38/MSK1. Mixed-lineage kinase 3 (MLK3) is an upstream kinase of MKK4 and MKK3/6. Thus, we evaluated the effect of biochanin A on MLK3. We found that sUV-induced MLK3 phosphorylation was not affected, whereas MLK3 kinase activity was significantly suppressed by biochanin A. Furthermore, direct binding of biochanin A in the MLK3 ATP-binding pocket was detected using pull-down assays. Computer modeling supported our observation that MLK3 is a novel target of biochanin A. These results suggest that biochanin A exerts chemopreventive effects by suppressing sUV-induced COX-2 expression mediated through MLK3 inhibition.
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