Melanoma accounts for only about 4% of all skin cancer cases but most of skin cancer‐related deaths. Standard systemic therapies such as interferon (IFN) have not been adequately effective in the management of melanoma. Therefore, novel approaches are needed for prevention and treatment of this disease. Chemoprevention by naturally occurring agents present in food and beverages has shown benefits in certain cancers including nonmelanoma skin cancers. Here, employing 2 human melanoma cell lines (A‐375 amelanotic malignant melanoma and Hs‐294T metastatic melanoma) and normal human epidermal melanocytes (NHEM), we studied the antiproliferative effects of epigallocatechin‐3‐gallate (EGCG), the major polyphenolic antioxidant present in green tea. EGCG treatment was found to result in a dose‐dependent decrease in the viability and growth of both melanoma cell lines. Interestingly, at similar EGCG concentrations, the normal melanocytes were not affected. EGCG treatment of the melanoma cell lines resulted in decreased cell proliferation (as assessed by Ki‐67 and PCNA protein levels) and induction of apoptosis (as assessed cleavage of PARP, TUNEL assay and JC‐1 assay). EGCG also significantly inhibited the colony formation ability of the melanoma cells studied. EGCG treatment of melanoma cells resulted in a downmodulation of anti‐apoptotic protein Bcl2, upregulation of proapoptotic Bax and activation of caspases ‐3, ‐7 and ‐9. Furthermore, our data demonstrated that EGCG treatment resulted in a significant, dose‐dependent decrease in cyclin D1 and cdk2 protein levels and induction of cyclin kinase inhibitors (ckis) p16^INK4a, p21^WAF1/CIP1 and p27^KIP1. Our data suggest that EGCG causes significant induction of cell cycle arrest and apoptosis of melanoma cells that is mediated via modulations in the cki‐cyclin‐cdk network and Bcl2 family proteins. Thus, EGCG, alone or in conjunction with current therapies, could be useful for the management of melanoma.

Cutaneous T-cell lymphoma (CTCL) is a hematologic malignant disease whose most common variant, mycosis fungoides, is characterized by flat cutaneous patches that become progressively infiltrated to form plaques and tumors.¹ Extracutaneous tissues can become involved in the later stages of disease. Sézary syndrome is the term given to the leukemic variant of CTCL when accompanied by erythroderma. Considerable evidence suggests that early CTCL has apoptotic defects that render it more of a lymphoaccumulative disorder than a lymphoproliferative disorder.^2-10 This includes a low apoptotic rate, low proliferative rate, relatively indolent clinical course, and no enhanced survival following conventional chemotherapy.

Melanoma incidences have increased over the last few decades and metastatic melanoma is one of the hardest malignancies to treat. Thus, novel approaches are needed for an effective management of me...

This article reviews methotrexate and the more potent, related compound, pralatrexate, for the treatment of cutaneous T-cell lymphomas, including mycosis fungoides, Sézary syndrome, and CD30+ lymphoproliferative disorders. Although these folate antagonists are traditionally viewed as antiproliferative cell cycle inhibitors, it is recognized that they inhibit DNA methylation, providing a rationale for their use as epigenetic regulators and cell proliferation inhibitors. The underlying mechanisms are outlined, key supporting data presented, followed by brief mention of recent mathematical modeling supporting the general superiority of combination therapy. Several novel examples involving folate antagonists are proposed.