BackgroundMelanogenesis is one of the characteristic parameters of differentiation in melanocytes and melanoma cells. Specific inhibitors of phosphatidylinositol 3-kinase (PI3K), such as wortmannin and LY294002, stimulate melanin production in mouse and in human melanoma cells, suggesting that PI3K and mammalian target of rapamycin (mTOR) might be involved in the regulation of melanogenesis.ObjectiveThe involvement of the mTOR pathway in regulating melanogenesis was examined using human MNT-1 melanoma cells, and the effects of the potent inhibitor of mTOR, rapamycin, in the presence or absence of α-melanocyte-stimulating hormone (α-MSH) were evaluated.MethodsIn cells treated with rapamycin, cell viability, melanin content, and tyrosinase (TYR) activity were measured and compared with untreated controls. Protein levels of TYR, tyrosinase-related protein (TYRP)-1, TYRP-2, and microphthalmia-associated transcription factor (MITF) were also analyzed by Western blot.ResultsIn rapamycin-treated cells, the melanin content increased concomitantly with an elevation in TYR activity, which plays a major role in melanogenesis. There was also an up-regulation of TYR, TYRP-1, and MITF proteins. Combined treatment with rapamycin or wortmannin and α-MSH increased melanogenesis more strongly than α-MSH alone.ConclusionRapamycin-induced melanin formation may be mediated through the up-regulation of TYR protein and activity. Furthermore, rapamycin and wortmannin, inhibitors of mTOR and PI3K, respectively, have co-stimulatory effects with α-MSH in enhancing melanogenesis in melanocyte cells.

Procyanidins can inhibit cell proliferation and tumorigenesis and induce apoptosis in human skin, breast and prostate carcinoma cell lines. Squamous cell carcinoma (SCC) of the skin is a common form of keratinocytic or non-melanoma skin cancer and is a deadly disease with a poor prognosis due to the ineffectiveness of therapy. The present study aimed to determine whether grape seed proanthocyanidin (GSP) may regulate different modes of cell death in the human SCC12 cell line. The present study found that the treatment of SCC12 cells with GSP inhibited proliferation in a dose-dependent manner and reduced the motility and invasiveness of SCC12 cells through suppression of matrix metalloproteinase-2/9 expression. GSP treatment also resulted in induction of apoptosis and autophagy via generation of reactive oxygen species. The inhibition of autophagy by 3-methyladenine decreased GSP-induced cell death, which suggested that GSP-induced autophagy can promote cell death. The results of the present study suggested that autophagy functions as a death mechanism in SCC and provided a rationale for the use of GSP in combination with autophagy activators for treating cancers such as SCC.

Lichen sclerosus is a chronic inflammatory mucocutaneous disorder predominately affecting prepubertal girls and postmenopausal women. Isolated lichen sclerosus affecting the oral mucosa is exceedingly rare, and only 13 patients with biopsy-proved isolated oral disease have been reported in the literature. We report on a 7-year-old Korean girl with a well-demarcated 1.2×1.2 cm atrophic white plaque with an erythematous border and focal telangiectasia on the left vermillion lip, extending to the labial mucosa. No other cutaneous surfaces, including genitalia, were involved. An incisional biopsy of the plaque on the lip revealed a patchy lichenoid infiltrate of lymphocytes associated with sclerosis of the papillary dermis and a thinned epidermis consistent with a diagnosis of linear orofacial lichen sclerosus. Treatment with a short course of 1% pimecrolimus cream effectively prevented the progression of this lesion.

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We report a rare case of granuloma annulare (GA), affecting both ear antihelixes, in a 28-year old male patient that presented with a 1-year history of non-tender, firm, skin-colored, 1∼5 mm papules on both ear antihelixes. There was no history of trauma. An excisional biopsy specimen taken from one of the lesions of the right ear revealed infiltration of histiocytes and lymphocytes around a zone of collagen alteration in the dermis. Based on the clinical and pathological findings, the patient was diagnosed with a rare case of bilateral GA of both antihelixes; this is the first report in the Korean dermatology literature.