Phytol suppresses melanogenesis through proteasomal degradation of MITF via the ROS-ERK signaling pathway

Ko, Gyeong‐A; Cho, Somi Kim

doi:10.1016/j.cbi.2018.02.033

Cited by 35 publications

(28 citation statements)

References 58 publications

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“…Regarding the antimelanogenic effect of EO components, the study of Lin JH's group reported the ability of zerumbrone to decrease melanin accumulation in B16-F10 cells, and to suppress the expression of MITF and its target genes, TYRP1 and TYRP2, after MSH stimulation with a mechanism involving ERK1/2, but not the PKA-CREB signaling pathway [226]. Antimelanogenic activity in the same melanoma model through ubiquitination and proteasomal degradation of MITF, in a ROS/ERK-dependent way, was also reported for phytol [223]. Valencene one of the major constituents of Ocotea dispersa EO decreased melanin content after UVB irradiation in B16-F10 cells [225].…”

Section: Antimelanogenic Activitymentioning

confidence: 78%

Essential Oils and Their Main Chemical Components: The Past 20 Years of Preclinical Studies in Melanoma

Martile

Garzoli

Ragno

et al. 2020

Cancers

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The last two decades have seen the development of effective therapies, which have saved the lives of a large number of melanoma patients. However, therapeutic options are still limited for patients without BRAF mutations or in relapse from current treatments, and severe side effects often occur during therapy. Thus, additional insights to improve treatment efficacy with the aim to decrease the likelihood of chemoresistance, as well as reducing side effects of current therapies, are required. Natural products offer great opportunities for the discovery of antineoplastic drugs, and still represent a useful source of novel molecules. Among them, essential oils, representing the volatile fraction of aromatic plants, are always being actively investigated by several research groups and show promising biological activities for their use as complementary or alternative medicine for several diseases, including cancer. In this review, we focused on studies reporting the mechanism through which essential oils exert antitumor action in preclinical wild type or mutant BRAF melanoma models. We also discussed the latest use of essential oils in improving cancer patients’ quality of life. As evidenced by the many studies listed in this review, through their effect on apoptosis and tumor progression-associated properties, essential oils can therefore be considered as potential natural pharmaceutical resources for cancer management.

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Section: Antimelanogenic Activitymentioning

confidence: 78%

Essential Oils and Their Main Chemical Components: The Past 20 Years of Preclinical Studies in Melanoma

Martile

Garzoli

Ragno

et al. 2020

Cancers

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“…MAPK family proteins, including ERK1/2, JNK, and p38, play an important role in melanin synthesis. Recent studies have shown that ERK phosphorylation degrades MITF by ubiquitination and inhibits TYR and TRP-1,2 expression, whereas JNK and p38 phosphorylation increases MITF expression, thereby inducing TYR and TRP-1,2 upregulation [26,27,28]. In addition, phosphorylated AKT has been implicated in melanin synthesis inhibition by phosphorylating MITF [29].…”

Section: Resultsmentioning

confidence: 99%

Tobramycin Promotes Melanogenesis by Upregulating p38 MAPK Protein Phosphorylation in B16F10 Melanoma Cells

2019

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Tobramycin is an aminoglycoside-based natural antibiotic derived from Streptomyces tenebrarius, which is primarily used for Gram-negative bacterial infection treatment. Although tobramycin has been utilized in clinical practice for a long time, it has exhibited several side effects, leading to the introduction of more effective antibiotics. Therefore, we conducted our experiments focusing on new possibilities for the clinical use of tobramycin. How tobramycin affects skin melanin formation is unknown. This study used B16F10 melanoma cells to assess the effect of tobramycin on melanin production. After cytotoxicity was assessed by MTT assay, melanin content and tyrosinase activity analyses revealed that tobramycin induces melanin synthesis in B16F10 cells. Next, Western blot analyses were performed to elucidate the mechanism by which tobramycin increases melanin production; phosphorylated p38 protein expression was upregulated. Protein inhibitors have been used to elucidate the mechanism of tobramycin. Kanamycin A and B are structurally similar to tobramycin, and 2-DOS represents the central structure of these antibiotics. The effects of these substances on melanogenesis were evaluated. Kanamycin A reduced melanin production, whereas kanamycin B and 2-DOS had no effect. Overall, our data indicated that tobramycin increases melanin production by promoting p38 protein phosphorylation in B16F10 melanoma cells.

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“…It stimulates ROS production in B16F10 murine melanoma cells. This radical burst reduces melanogenesis via phosphorylation of the extracellular signal-regulated protein kinase (ERK) which in turn induces the proteasomal degradation of MITF [27].…”

Section: 1mentioning

confidence: 99%

“…Biogenetically speaking they are a small group of diterpenes closely related to both labdane and clerodane diterpenoids [1]. One such compound, (5R,8R,9S,13R)-halim-1,10-ene-15,16-diol (27), was isolated from Vellozia kolbekii Alves (Velloziaceae) and showed cytotoxicity against three human cancer cell lines, including MDA-MB-435 by a mechanism of action involving cell cycle arrest at the S/G2M phases [57].…”

Section: 6mentioning

confidence: 99%

Natural Cytotoxic Diterpenoids, a Potential Source of Drug Leads for Melanoma Therapy

Prieto

Silveira

2019

CPD

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Diterpenes present complex structure and due to their unique carbon skeleton and interesting biological activities, have been the focus of continuous studies for the development of new anticancer agents. Phorbol esters have been known for their activity against skin malignancies since ancient times. Taxol was first studied in melanoma cells, and recently ingenol mebutate has been approved for the chemoprevention of melanoma in actinic keratosis patients. Therefore, there is scope for research on this class of compounds. We here aim to review the relevant original research reporting on isolated diterpenes with cytotoxic and/or antitumoral activities upon melanoma cells. By collating and discussing the implications of past and current developments on diterpenes, we hope to steer further interest on this field and facilitate the drug discovery activities of the scientific community towards finding potential alternatives to current melanoma chemotherapy.

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Phytol suppresses melanogenesis through proteasomal degradation of MITF via the ROS-ERK signaling pathway

Cited by 35 publications

References 58 publications

Essential Oils and Their Main Chemical Components: The Past 20 Years of Preclinical Studies in Melanoma

Essential Oils and Their Main Chemical Components: The Past 20 Years of Preclinical Studies in Melanoma

Tobramycin Promotes Melanogenesis by Upregulating p38 MAPK Protein Phosphorylation in B16F10 Melanoma Cells

Natural Cytotoxic Diterpenoids, a Potential Source of Drug Leads for Melanoma Therapy

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