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Biology subjects

Owens, D. M.

Publications and source records attributed to Owens, D. M..

2 recordsLinked to original sources

Camphor white oil induces tumor regression through cytotoxic T cell-dependent mechanisms

Bioactive derivatives from the camphor laurel tree, Cinnamomum camphora, are posited to exhibit chemopreventive properties but the efficacy and mechanism of these natural products have not been established. We tested an essential-oil derivative, camphor white oil (CWO), for anti-tumor activity in a mouse model of keratinocyte-derived skin cancer. Daily topical treatment with CWO induced dramatic regression of pre-malignant skin tumors and a two-fold reduction in cutaneous squamous cell carcinomas. We next investigated underlying cellular and molecular mechanisms. In cultured keratinocytes, CWO stimulated calcium signaling, resulting in calcineurin-dependent activation of nuclear factor of activated T cells (NFAT). In vivo, CWO induced transcriptional changes in immune-related genes, resulting in cytotoxic T cell-dependent tumor regression. Finally, we identified chemical constituents of CWO that recapitulated effects of the admixture. Together, these studies identify T cell-mediated tumor regression as the mechanism through which a plant-derived essential oil diminishes established tumor burden.\n\nSUMMARY BLURBEssential oil derived from the camphor tree acts by stimulating immune cell-dependent regression of skin tumors in a mouse model of cutaneous squamous cell carcinoma.

physiology

2-APB arrests human keratinocyte proliferation and inhibits cutaneous squamous cell carcinoma in vitro

BackgroundThe epidermis is a stratified epithelium whose differentiation program is triggered in part by calcium. Dysregulation of keratinocyte differentiation may lead to non-melanoma skin cancers, including cutaneous squamous cell carcinoma (cSCC). The compound 2-aminoethoxydiphenyl borate (2-APB) modulates calcium signaling by altering activity of calcium-permeable channels of the transient receptor potential (TRP) and ORAI families, and is therefore poised to govern signaling pathways that control the balance of keratinocyte proliferation and differentiation.\n\nObjectiveWe sought to determine whether 2-APB alters differentiation of normal human keratinocytes and progression of human cSCCs models in vitro.\n\nMethodsPrimary human keratinocyte cultures were treated with 2-APB and levels of proliferation (EdU incorporation) and differentiation markers [quantitative PCR (qPCR)] were assessed. Human cSCC biopsies and cell lines were analyzed for TRP and ORAI gene expression via qPCR. cSCC cell lines were cultured in organtypic cultures and analyzed for growth and invasiveness after 2-APB or vehicle treatment.\n\nResultsCulturing human keratinocytes with 2-APB arrested cell proliferation, triggered differentiation-gene expression and altered epidermal stratification, indicating that 2-APB application is sufficient to promote differentiation. In human organotypic cSCC cultures, 2-APB attenuated tumor growth and invasiveness. Finally, expression of a panel of 2-APB-targeted ion channels (TRPV3, TRPV1, TRPC1, OraI1, OraI2 and OraI3) was dysregulated in high-risk cSCC biopsies.\n\nConclusionsCollectively, these findings identify 2-APB as a potential therapeutic for high-risk cSCCs.

cell biology