Little is known on the difference in the incidence of vulvar and vaginal melanomas in various racial/ethnic groups. Population-based incidence of these melanomas in Asian and Hispanic individuals is almost unknown. Using 1992–2005 data provided by the National Cancer Institute's Surveillance, Epidemiology, and End Results Program, we calculated age-adjusted incidence rates of vulvar and vaginal melanomas in various racial/ethnic groups. From 1992 to 2005, there were 324 vulvar melanomas and 125 vaginal melanomas diagnosed in this group. The annual age-adjusted incidence rates (per million female population) of vulvar and vaginal melanomas in the different racial/ethnic groups was 0.87 (Blacks), 0.75 (American–Indian), 1.03 (Asians and Pacific Islanders), 1.22 (Hispanics), and 1.90 (non-Hispanic Whites). The overall white/black incidence ratio in vulvar and vaginal melanomas was 3.14 : 1 and 1.02 : 1, respectively; which is much less than that of cutaneous melanoma (13 : 1–17 : 1) and uveal melanoma (18 : 1) and is similar to that of conjunctival melanoma (2.6 : 1) and other mucosal melanomas (2.1 : 1–2.3 : 1). The low racial difference in vulvar and vaginal melanomas (as well as conjunctival and other mucosal melanomas) may be determined by their microenvironment factors (all originate from mucosa or semi-mucosa tissues). The incidence of vulvar and vaginal melanomas has does not increased in recent decades or toward the south (more sun exposure), indicating that ultraviolet radiation is not a causative factor in these melanomas. The slight decrease of incidence of vulvar melanoma in dark pigmented individuals may be related to the biochemical protective effects of melanin (as an antioxidant) rather than their photo-screen effects.

Natural bioactives or phytochemicals are generally referred to as the compounds that have specific biological activity in human. Studies have shown that natural phytochemicals derived from certain plants have the capability to prevent carcinogenesis. In this special issue, we collected numerous studies which provide novel evidence to support the opinion. For instance, [6]-gingerol prevents disassembly of cell junctions and activities of MMPs in invasive human pancreas cancer cells; butein inhibits angiogenesis of human endothelial progenitor cells; the anticancer effects of sterol fraction come from red algae porphyra dentata; zeaxanthin induces apoptosis in human uveal melanoma cells; and ocotillol enhanced the antitumor activity of doxorubicin. It is therefore believed that the appropriate application of natural bioactives or phytochemicals should be a supplementary and safe way to prevent carcinogenesis and/or to enhance the efficacy of cancer therapy.

The cytotoxic effects of zeaxanthin on two human uveal melanoma cell lines (SP6.5 and C918) and related signaling pathways were studied and compared to effects on normal ocular cells (uveal melanocytes, retinal pigment epithelial cells, and scleral fibroblasts). MTT assay revealed that zeaxanthin reduced the cell viability of melanoma cells in a dose-dependent manner (10, 30, and 100 μM), with IC₅₀at 40.8 and 28.7 μM in SP6.5 and C918 cell lines, respectively. Zeaxanthin did not affect the viability of normal ocular cells even at the highest levels tested (300 μM), suggesting that zeaxanthin has a selectively cytotoxic effect on melanoma cells. Zeaxanthin induced apoptosis in melanoma cells as indicated by annexin V and ethidium III flow cytometry. Western blot analysis demonstrated that zeaxanthin decreased the expression of antiapoptotic proteins (Bcl-2 and Bcl-xL) and increased the expression of proapoptotic proteins (Bak and Bax) in zeaxanthin-treated melanoma cells. Zeaxanthin increased mitochondrial permeability as determined by JC-1 fluorescein study. Zeaxanthin also increased the level of cytosol cytochrome c and caspase-9 and -3 activities, but not caspase-8, as measured by ELISA assay or colorimetric assay. All of these findings indicate that the intrinsic (mitochondrial) pathway is involved in zeaxanthin-induced apoptosis in uveal melanoma cells.