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Natural tyrosinase enzyme inhibitors: A path from melanin to melanoma and its reported pharmacological activities

Rajan Logesh, Sagar Rajendra Prasad, Sandhya Chipurupalli, Nirmal Robinson, Suresh Mohankumar Orcid Logo

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume: 1878, Issue: 6, Start page: 188968

Swansea University Author: Suresh Mohankumar Orcid Logo

  • Accepted Manuscript under embargo until: 30th August 2024

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DOI (Published version): 10.1016/j.bbcan.2023.188968

Abstract

The skin containing melanin pigment acts as a protective barrier and counteracts the UVR and other environmental stressors to maintain or restore disrupted cutaneous homeostasis. The production of melanin pigment is dependent on tyrosine levels. L-tyrosine and L-dihydroxyphenylalanine (L-DOPA) can s...

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Published in: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
ISSN: 0304-419X 1879-2561
Published: Elsevier BV 2023
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URI: https://cronfa.swan.ac.uk/Record/cronfa64807
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spelling v2 64807 2023-10-24 Natural tyrosinase enzyme inhibitors: A path from melanin to melanoma and its reported pharmacological activities edce0da45e3933d3460963b966f4c84e 0000-0001-8862-2979 Suresh Mohankumar Suresh Mohankumar true false 2023-10-24 PHAR The skin containing melanin pigment acts as a protective barrier and counteracts the UVR and other environmental stressors to maintain or restore disrupted cutaneous homeostasis. The production of melanin pigment is dependent on tyrosine levels. L-tyrosine and L-dihydroxyphenylalanine (L-DOPA) can serve both as a substrates and intermediates of melanin synthetic pathway and as inducers and positive regulators of melanogenesis. The biosynthesis of melanin is stimulated upon exposure to UVR, which can also stimulate local production of hormonal factors, which can stimulate melanoma development by altering the chemical properties of eu- and pheomelanin. The process of melanogenesis can be altered by several pathways. One involves activation of POMC, with the production of POMC peptides including MSH and ACTH, which increase intracellular cAMP levels, which activates the MITF, and helps to stimulate tyrosinase (TYR) expression and activity. Defects in OCA1 to 4 affects melanogenic activity via posttranslational modifications resulting in proteasomal degradation and reducing pigmentation. Further, altering, the MITF factor, helps to regulate the expression of MRGE in melanoma, and helps to increase the TYR glycosylation in ER. CRH stimulates POMC peptides that regulate melanogenesis and also by itself can stimulate melanogenesis. The POMC, P53, ACTH, MSH, MC1R, MITF, and 6-BH4 are found to be important regulators for pigmentation. Melanogenesis can affect melanoma behaviour and inhibit immune responses. Therefore, we reviewed natural products that would alter melanin production. Our special focus was on targeting melanin synthesis and TYR enzyme activity to inhibit melanogenesis as an adjuvant therapy of melanotic melanoma. Furthermore, this review also outlines the current updated pharmacological studies targeting the TYR enzyme from natural sources and its consequential effects on melanin production. Journal Article Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1878 6 188968 Elsevier BV 0304-419X 1879-2561 Melanoma, Tyrosinase inhibitors, Melanin, Melanogenesis, Skin pigmentation, Skin cancer 1 11 2023 2023-11-01 10.1016/j.bbcan.2023.188968 COLLEGE NANME Pharmacy COLLEGE CODE PHAR Swansea University Another institution paid the OA fee 2024-04-16T10:21:53.1296602 2023-10-24T12:47:42.1387332 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Pharmacy Rajan Logesh 1 Sagar Rajendra Prasad 2 Sandhya Chipurupalli 3 Nirmal Robinson 4 Suresh Mohankumar 0000-0001-8862-2979 5 Under embargo Under embargo 2023-11-15T15:56:38.4825696 Output 3228343 application/pdf Accepted Manuscript true 2024-08-30T00:00:00.0000000 Released under the terms of a CC-BY-NC-ND license. true eng https://creativecommons.org/licenses/by-nc-nd/4.0/deed.en
title Natural tyrosinase enzyme inhibitors: A path from melanin to melanoma and its reported pharmacological activities
spellingShingle Natural tyrosinase enzyme inhibitors: A path from melanin to melanoma and its reported pharmacological activities
Suresh Mohankumar
title_short Natural tyrosinase enzyme inhibitors: A path from melanin to melanoma and its reported pharmacological activities
title_full Natural tyrosinase enzyme inhibitors: A path from melanin to melanoma and its reported pharmacological activities
title_fullStr Natural tyrosinase enzyme inhibitors: A path from melanin to melanoma and its reported pharmacological activities
title_full_unstemmed Natural tyrosinase enzyme inhibitors: A path from melanin to melanoma and its reported pharmacological activities
title_sort Natural tyrosinase enzyme inhibitors: A path from melanin to melanoma and its reported pharmacological activities
author_id_str_mv edce0da45e3933d3460963b966f4c84e
author_id_fullname_str_mv edce0da45e3933d3460963b966f4c84e_***_Suresh Mohankumar
author Suresh Mohankumar
author2 Rajan Logesh
Sagar Rajendra Prasad
Sandhya Chipurupalli
Nirmal Robinson
Suresh Mohankumar
format Journal article
container_title Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
container_volume 1878
container_issue 6
container_start_page 188968
publishDate 2023
institution Swansea University
issn 0304-419X
1879-2561
doi_str_mv 10.1016/j.bbcan.2023.188968
publisher Elsevier BV
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Pharmacy{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Pharmacy
document_store_str 0
active_str 0
description The skin containing melanin pigment acts as a protective barrier and counteracts the UVR and other environmental stressors to maintain or restore disrupted cutaneous homeostasis. The production of melanin pigment is dependent on tyrosine levels. L-tyrosine and L-dihydroxyphenylalanine (L-DOPA) can serve both as a substrates and intermediates of melanin synthetic pathway and as inducers and positive regulators of melanogenesis. The biosynthesis of melanin is stimulated upon exposure to UVR, which can also stimulate local production of hormonal factors, which can stimulate melanoma development by altering the chemical properties of eu- and pheomelanin. The process of melanogenesis can be altered by several pathways. One involves activation of POMC, with the production of POMC peptides including MSH and ACTH, which increase intracellular cAMP levels, which activates the MITF, and helps to stimulate tyrosinase (TYR) expression and activity. Defects in OCA1 to 4 affects melanogenic activity via posttranslational modifications resulting in proteasomal degradation and reducing pigmentation. Further, altering, the MITF factor, helps to regulate the expression of MRGE in melanoma, and helps to increase the TYR glycosylation in ER. CRH stimulates POMC peptides that regulate melanogenesis and also by itself can stimulate melanogenesis. The POMC, P53, ACTH, MSH, MC1R, MITF, and 6-BH4 are found to be important regulators for pigmentation. Melanogenesis can affect melanoma behaviour and inhibit immune responses. Therefore, we reviewed natural products that would alter melanin production. Our special focus was on targeting melanin synthesis and TYR enzyme activity to inhibit melanogenesis as an adjuvant therapy of melanotic melanoma. Furthermore, this review also outlines the current updated pharmacological studies targeting the TYR enzyme from natural sources and its consequential effects on melanin production.
published_date 2023-11-01T10:21:51Z
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score 11.012678

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