Minocycline Impact on Redox Homeostasis of Normal Human Melanocytes HEMn-LP Exposed to UVA Radiation and Hydrogen Peroxide

Rok, Jakub; Rzepka, Zuzanna; Maszczyk, Mateusz; Beberok, Artur; Wrześniok, Dorota

doi:10.3390/ijms22041642

Cited by 8 publications

(13 citation statements)

References 91 publications

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“…Lightly pigmented melanocytes were more sensitive to minocycline. In this case, EC 50 was calculated to be about 48 µM [ 49 ]. The observed difference for darkly and lightly pigmented melanocytes suggests that a high content of melanin may protect cells from the tetracycline-induced adverse effect.…”

Section: Discussionmentioning

confidence: 99%

The Anticancer Potential of Doxycycline and Minocycline—A Comparative Study on Amelanotic Melanoma Cell Lines

Rok

Rzepka

Kowalska

et al. 2022

IJMS

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Malignant melanoma is still a serious medical problem. Relatively high mortality, a still-growing number of newly diagnosed cases, and insufficiently effective methods of therapy necessitate melanoma research. Tetracyclines are compounds with pleiotropic pharmacological properties. Previously published studies on melanotic melanoma cells ascertained that minocycline and doxycycline exerted an anti-melanoma effect. The purpose of the study was to assess the anti-melanoma potential and mechanisms of action of minocycline and doxycycline using A375 and C32 human amelanotic melanoma cell lines. The obtained results indicate that the tested drugs inhibited proliferation, decreased cell viability, and induced apoptosis in amelanotic melanoma cells. The treatment caused changes in the cell cycle profile and decreased the intracellular level of reduced thiols and mitochondrial membrane potential. The exposure of A375 and C32 cells to minocycline and doxycycline triggered the release of cytochrome c and activated initiator and effector caspases. The anti-melanoma effect of analyzed drugs appeared to be related to the up-regulation of ERK1/2 and MITF. Moreover, it was noticed that minocycline and doxycycline increased the level of LC3A/B, an autophagy marker, in A375 cells. In summary, the study showed the pleiotropic anti-cancer action of minocycline and doxycycline against amelanotic melanoma cells. Considering all results, it could be concluded that doxycycline was a more potent drug than minocycline.

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Section: Discussionmentioning

confidence: 99%

The Anticancer Potential of Doxycycline and Minocycline—A Comparative Study on Amelanotic Melanoma Cell Lines

Rok

Rzepka

Kowalska

et al. 2022

IJMS

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“…It is worth mentioning that lightly pigmented melanocytes (HEMn-LP) appeared to be more sensitive to minocycline. Recently published study indicated the EC 50 value was two-times lower for lightly pigmented melanocytes then obtained for darkly pigmented cells [44]. The difference suggests that melanin may protect cells from toxic effects of minocycline.…”

Section: Discussionmentioning

confidence: 91%

Molecular and Biochemical Basis of Minocycline-Induced Hyperpigmentation—The Study on Normal Human Melanocytes Exposed to UVA and UVB Radiation

Rok

Rzepka

Kowalska

et al. 2021

IJMS

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Minocycline is a drug which induces skin hyperpigmentation. Its frequency reaches up to 50% of treated patients. The adverse effect diminishes the great therapeutic potential of minocycline, including antibacterial, neuroprotective, anti-inflammatory and anti-cancer actions. It is supposed that an elevated melanin level and drug accumulation in melanin-containing cells are related to skin hyperpigmentation. This study aimed to evaluate molecular and biochemical mechanism of minocycline-induced hyperpigmentation in human normal melanocytes, as well as the contribution of UV radiation to this side effect. The experiments involved the evaluation of cyto- and phototoxic potential of the drug using cell imaging with light and confocal microscopes as well as biochemical and molecular analysis of melanogenesis. We showed that minocycline induced melanin synthesis in epidermal melanocytes. The action was intensified by UV irradiation, especially with the UVB spectrum. Minocycline stimulated the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase (TYR) gene. Higher levels of melanin and increased activity of tyrosinase were also observed in treated cells. Moreover, minocycline triggered the supranuclear accumulation of tyrosinase, similar to UV radiation. The decreased level of premelanosome protein PMEL17 observed in all minocycline-treated cultures suggests disorder of the formation, maturation or distribution of melanosomes. The study revealed that minocycline itself was able to enhance melanin synthesis. The action was intensified by irradiation, especially with the UVB spectrum. Demonstrated results confirmed the potential role of melanin and UV radiation minocycline-induced skin hyperpigmentation.

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“…Our preliminary study of minocycline revealed that the drug significantly increased melanin content and the activity of tyrosinase—the key enzyme of melanogenesis. Besides, it triggered the supranuclear accumulation of tyrosinase, similar to UVA and UVB radiation [ 75 , 76 ].…”

Section: Chemical and Biological Basis Of Photosensitivitymentioning

confidence: 99%

Drug-Induced Photosensitivity—From Light and Chemistry to Biological Reactions and Clinical Symptoms

et al. 2021

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Photosensitivity is one of the most common cutaneous adverse drug reactions. There are two types of drug-induced photosensitivity: photoallergy and phototoxicity. Currently, the number of photosensitization cases is constantly increasing due to excessive exposure to sunlight, the aesthetic value of a tan, and the increasing number of photosensitizing substances in food, dietary supplements, and pharmaceutical and cosmetic products. The risk of photosensitivity reactions relates to several hundred externally and systemically administered drugs, including nonsteroidal anti-inflammatory, cardiovascular, psychotropic, antimicrobial, antihyperlipidemic, and antineoplastic drugs. Photosensitivity reactions often lead to hospitalization, additional treatment, medical management, decrease in patient’s comfort, and the limitations of drug usage. Mechanisms of drug-induced photosensitivity are complex and are observed at a cellular, molecular, and biochemical level. Photoexcitation and photoconversion of drugs trigger multidirectional biological reactions, including oxidative stress, inflammation, and changes in melanin synthesis. These effects contribute to the appearance of the following symptoms: erythema, swelling, blisters, exudation, peeling, burning, itching, and hyperpigmentation of the skin. This article reviews in detail the chemical and biological basis of drug-induced photosensitivity. The following factors are considered: the chemical properties, the influence of individual ranges of sunlight, the presence of melanin biopolymers, and the defense mechanisms of particular types of tested cells.

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Minocycline Impact on Redox Homeostasis of Normal Human Melanocytes HEMn-LP Exposed to UVA Radiation and Hydrogen Peroxide

Cited by 8 publications

References 91 publications

The Anticancer Potential of Doxycycline and Minocycline—A Comparative Study on Amelanotic Melanoma Cell Lines

The Anticancer Potential of Doxycycline and Minocycline—A Comparative Study on Amelanotic Melanoma Cell Lines

Molecular and Biochemical Basis of Minocycline-Induced Hyperpigmentation—The Study on Normal Human Melanocytes Exposed to UVA and UVB Radiation

Drug-Induced Photosensitivity—From Light and Chemistry to Biological Reactions and Clinical Symptoms

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