Mechanism of Pigmentation by Minocycline in Murine B16 Melanoma Cells

Abstract

Long-term treatment with minocycline is known to induce pigmentation or discoloration in tissues but how remains unclear. We investigated the mechanism of pigmentation using B16 melanoma cells. First, we conˆrmed that intracellular melanin levels increased on minocycline treatment. Then, using the reverse transcriptase-polymerase chain reaction (RT-PCR), we found the expression of mRNA of tyrosinase, tyrosinase-related protein (TRP)-1 and TRP-2, to also be signiˆcantly increased by treatment with minocycline at 5 mg/ml for 72 h. These results suggest that the minocycline-induced stimulation of melanogenesis occurs at the transcriptional level. Western-blotting revealed slight phosphorylation of extracellular signal-regulated kinase (ERK) 30 60 min after the minocycline treatment. The mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor U0126 and the p38 inhibitor SB203580 were used to examine the signaling pathway associated with the mRNA expression of tyrosinase, TRP-1, or TRP-2 when B16 melanoma cells were treated with minocycline. The SB203580 inhibited the mRNA expression of tyrosinase and TRP-1, suggesting the minocyclineinduced melanogensis occurred via a p38 signaling pathway.

Effects of the melanogenic inhibitor, uracil, derived from Lactobacillus plantarum TWK10-fermented soy milk on anti-melanogenesis in B16F0 mouse melanoma cells

“…The past two decades have brought an enormous increase in our understanding of melanogenic enzymes, of melanosomes, and of the intracellular and intercellular signaling pathways that regulate pigmentation (Park, Kosmadaki, Yaar, & Gilchrest, 2009). The B16 mouse melanoma cell line is used extensively for melanogenic studies and is considered a stable cell line for studying melanin production (Kim et al, 2014;Sato, Tsukimoto, Shimura, Awaya, & Kojima, 2011;Yao, Oh, Oh, Park, & Chung, 2013).…”

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

“…It is difficult to unambiguously indicate the reason or mechanism for minocyclineinducing redox imbalance. Among the possible causes can be mentioned: (i) direct influence of minocycline on the antioxidant system or ROS production, (ii) the ability of minocycline to induce melanogenesis which could be also the source of ROS, and (iii) the impairment of mitochondrial function by the drug [67,68]. The conducted studies showed that minocycline caused, e.g., mitochondrial depolarization and permeabilized the inner mitochondrial membrane by forming ion channels [68,69].…”

A case of latanoprost‐induced diffuse facial skin hyperpigmentation

“…Dutkiewicz, Albert and Levin also reported latanoprost did not increase the mitotic index of human cutaneous melanoma cell lines. When it comes to minocycline‐induced hyperpigmentation, although not completely elucidated, the increase in the expression of tyrosinase, TRP‐1 and TRP‐2 and activation of p38 MAPK are thought to cause the side effect . Further molecular study on latanoprost‐induced hyperpigmentation is worth to practice.…”