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Drug repurposing and/or repositioning is an alternative method to develop new treatment for certain diseases. Albendazole was originally developed as an anthelmintic medication, and it has been used to treat a variety of parasitic infestations. In this study, we investigated the antitumor effect of albendazole and putative action mechanism. Results showed that albendazole dramatically decreased the cell viability of SCC cell lines (SCC12 and SCC13 cells). Albendazole increased apoptosis-related signals, including cleaved caspase-3 and PARP-1 in a dose-dependent fashion. The mechanistic study showed that albendazole induced endoplasmic reticulum (ER) stress, evidenced by increase of CHOP, ATF-4, caspase-4, and caspase-12. Pretreatment with ER stress inhibitor 4-PBA attenuated albendazole-induced apoptosis of SCC cells. In addition, albendazole decreased the colony-forming ability of SCC cells, together with inhibition of Wnt/β-catenin signaling. These results indicate that albendazole shows an antitumor effect via regulation of ER stress and cancer stemness, suggesting that albendazole could be repositioned for cutaneous SCC treatment. [ABSTRACT FROM AUTHOR]

Adiponectin plays important roles in metabolic function, inflammation and multiple biological activities in various tissues. However, evidence for adiponectin signaling in sebaceous glands is lacking, and its role remains to be clarified. This study investigated the role of adiponectin in lipid production in sebaceous glands in an experimental study of human sebocytes. We demonstrated that human sebaceous glands in vivo and sebocytes in vitro express adiponectin receptor and that adiponectin increased cell proliferation. Moreover, based on a lipogenesis study using Oil Red O, Nile red staining and thin layer chromatography, adiponectin strongly upregulated lipid production in sebocytes. In three-dimensional culture of sebocytes, lipid synthesis was markedly enhanced in sebocytes treated with adiponectin. This study suggested that adiponectin plays a significant role in human sebaceous gland biology. Adiponectin signaling is a promising target in the clinical management of barrier disorders in which sebum production is decreased, such as in atopic dermatitis and aged skin. [ABSTRACT FROM AUTHOR]

Imiquimod is known to exert its effects through Toll-like receptor 7 (TLR7) and/or TLR8, resulting in expression of proinflammatory cytokines and chemokines. Keratinocytes have not been reported to constitutively express TLR7 and TLR8, and the action of imiquimod is thought to be mediated by the adenine receptor, not TLR7 or TLR8. In this study, we revealed the expression of TLR7 in keratinocytes after calcium-induced differentiation. After addition of calcium to cultured keratinocytes, the immunological responses induced by imiquimod, such as activation of NF-κB and induction of TNF-α and IL-8, were more rapid and stronger. In addition, imiquimod induced the expression TLR7, and acted synergistically with calcium to induce proinflammatory cytokines. We confirmed that the responses induced by imiquimod were significantly inhibited by microRNAs suppressing TLR7 expression. These results suggest that TLR7 expressed in keratinocytes play key roles in the activation of NF-κB signaling by imiquimod, and that their modulation in keratinocytes could provide therapeutic potential for many inflammatory skin diseases. [ABSTRACT FROM AUTHOR]