Metabolism of Lumisterol2 by CYP27A1

Wu, Dalei; Nealon, Gareth L.; Liu, Yuchen; Kim, Tae Kang; Słomiński, Andrzej; Tuckey, Robert C.

doi:10.1016/j.jsbmb.2023.106370

Cited by 3 publications

(1 citation statement)

References 47 publications

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“…Interestingly, anti-melanoma activities in vitro have been demonstrated for vitamin D derivatives with a shortened or absent side chain (pregnacalciferols (pD) and pregnalumisterols (pL)) [ 410 , 443 , 449 , 469 , 473 , 474 , 484 , 588 ], which show reduced calcemic activity [ 599 ]. In addition, recently discovered lumisterol hydroxy metabolites have shown anti-melanoma activity in cell culture [ 464 , 465 , 496 , 600 ]. Of note, these compounds are non-calcemic.…”

Section: Role Of Vitamin D In Melanomamentioning

confidence: 99%

Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

Slominski,

Kim,

Janjetovic

et al. 2024

Cancers

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Melanoma, originating through malignant transformation of melanin-producing melanocytes, is a formidable malignancy, characterized by local invasiveness, recurrence, early metastasis, resistance to therapy, and a high mortality rate. This review discusses etiologic and risk factors for melanoma, diagnostic and prognostic tools, including recent advances in molecular biology, omics, and bioinformatics, and provides an overview of its therapy. Since the incidence of melanoma is rising and mortality remains unacceptably high, we discuss its inherent properties, including melanogenesis, that make this disease resilient to treatment and propose to use AI to solve the above complex and multidimensional problems. We provide an overview on vitamin D and its anticancerogenic properties, and report recent advances in this field that can provide solutions for the prevention and/or therapy of melanoma. Experimental papers and clinicopathological studies on the role of vitamin D status and signaling pathways initiated by its active metabolites in melanoma prognosis and therapy are reviewed. We conclude that vitamin D signaling, defined by specific nuclear receptors and selective activation by specific vitamin D hydroxyderivatives, can provide a benefit for new or existing therapeutic approaches. We propose to target vitamin D signaling with the use of computational biology and AI tools to provide a solution to the melanoma problem.

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Section: Role Of Vitamin D In Melanomamentioning

confidence: 99%

Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

Slominski,

Kim,

Janjetovic

et al. 2024

Cancers

Self Cite

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Biological Effects of CYP11A1-Derived Vitamin D and Lumisterol Metabolites in the Skin

Slominski,

Kim,

Janjetovic

et al. 2024

Journal of Investigative Dermatology

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Evolutionary formation of melatonin and vitamin D in early life forms: insects take centre stage

Kim,

Slominski,

Pyza

et al. 2024

Biological Reviews

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Melatonin, a product of tryptophan metabolism via serotonin, is a molecule with an indole backbone that is widely produced by bacteria, unicellular eukaryotic organisms, plants, fungi and all animal taxa. Aside from its role in the regulation of circadian rhythms, it has diverse biological actions including regulation of cytoprotective responses and other functions crucial for survival across different species. The latter properties are also shared by its metabolites including kynuric products generated by reactive oxygen species or phototransfomation induced by ultraviolet radiation. Vitamins D and related photoproducts originate from phototransformation of ∆5,7 sterols, of which 7‐dehydrocholesterol and ergosterol are examples. Their ∆5,7 bonds in the B ring absorb solar ultraviolet radiation [290–315 nm, ultraviolet B (UVB) radiation] resulting in B ring opening to produce previtamin D, also referred to as a secosteroid. Once formed, previtamin D can either undergo thermal‐induced isomerization to vitamin D or absorb UVB radiation to be transformed into photoproducts including lumisterol and tachysterol. Vitamin D, as well as the previtamin D photoproducts lumisterol and tachysterol, are hydroxylated by cyochrome P450 (CYP) enzymes to produce biologically active hydroxyderivatives. The best known of these is 1,25‐dihydroxyvitamin D (1,25(OH)2D) for which the major function in vertebrates is regulation of calcium and phosphorus metabolism. Herein we review data on melatonin production and metabolism and discuss their functions in insects. We discuss production of previtamin D and vitamin D, and their photoproducts in fungi, plants and insects, as well as mechanisms for their enzymatic activation and suggest possible biological functions for them in these groups of organisms. For the detection of these secosteroids and their precursors and photoderivatives, as well as melatonin metabolites, we focus on honey produced by bees and on body extracts of Drosophila melanogaster. Common biological functions for melatonin derivatives and secosteroids such as cytoprotective and photoprotective actions in insects are discussed. We provide hypotheses for the photoproduction of other secosteroids and of kynuric metabolites of melatonin, based on the known photobiology of ∆5,7 sterols and of the indole ring, respectively. We also offer possible mechanisms of actions for these unique molecules and summarise differences and similarities of melatoninergic and secosteroidogenic pathways in diverse organisms including insects.

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Metabolism of Lumisterol2 by CYP27A1

Cited by 3 publications

References 47 publications

Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

Biological Effects of CYP11A1-Derived Vitamin D and Lumisterol Metabolites in the Skin

Evolutionary formation of melatonin and vitamin D in early life forms: insects take centre stage

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