Impact of d‐δ‐Tocotrienol on Human A2058 and A375 Melanoma Cells

The rate‐limiting activity of the mevalonate pathway, 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG CoA) reductase, provides essential intermediates for the prenylation or dolichylation of growth‐related proteins including nuclear lamins, Ras and growth factor receptors. d ‐δ‐Tocotrienol, a post‐transcriptional down‐regulator of HMG CoA reductase, suppresses the proliferation of murine B16 melanoma cells and human blood, breast, cervix, colon, liver, lung, lymph gland, nerve , pancreas, and prostate tumor cells. Dietary d ‐δ‐tocotrienol suppresses the growth of implanted B16 melanomas without toxicity to host mice. We evaluated d ‐δ‐tocotrienol in human A2058 and A375 melanoma cells. d ‐δ‐Tocotrienol induced dose‐dependent suppression of the cell proliferation following 72 h incubation in 96‐well plates with IC50 values of 48 (A2058) and 22 (A375) μmol/L, respectively. Morphological changes detected by fluorescence microscopy following acridine orange and ethidium bromide dual staining showed d ‐δ‐tocotrienol‐induced apoptosis in A2058 cells. The impact of d ‐δ‐tocotrienol on A2058 cell proliferation was potentiated by lovastatin (IC50=3 μmol/L), a competitive inhibitor of HMG CoA reductase. d ‐δ‐Tocotrienol may have potential application in melanoma chemoprevention and/or therapy. TDA, TWU REP & Summer Stipend Award.