malignant melanoma is a malignancy arising from the transformation of melanocyte s, with increasing incidence worldwide. on the basis of the tissue where the primary lesion appears, four major subtypes can be disting uished: cutaneous melanoma ( non - glabrous skin ), acral melanoma ( glabrous skin ), mucosal melanoma ( melanocyte s in the mucosal tissues ), and uveal melanoma ( uveal tract of the eye ). among these major subtypes, it is possible to disting uish some particular variants: amelanotic / hypomelanotic melanoma, a subtype of cutaneous melanoma with low or absent melanin; desmoplastic melanoma, a spindle cell tumor exhibiting signs of dense scar - like fibrosis; spitzoid melanoma, sharing histopathological characteristics with spitz nevi; acral lentiginous melanoma, with a lentiginous growth pattern. ole seems to be effective in the prevention of skin carcinogenesis in vivo. orally administered 10 mg / kg and 25 mg / kg ole reduced skin carcinogenesis ( expressed in terms of number of tumors per mouse ) in uvb - irradiated albino hairless hos: hr - 1 mice. for 25 mg / kg ole, this effect was associated with a persistent reduction in ( i ) the total volume of tumors per mouse, ( ii ) the expression levels of invasion enzymes matrix metalloproteinase 2 ( mmp2 ), pro - mmp9, and mmp9, ( iii ) tissue angiogenesis marker vascular endothelial growth factor ( vegf ) and cyclooxygenase - 2 ( cox - 2 ) levels, and ( iv ) the percentage of skin ki - 67 + cells and platelet endothelial cell adhesion molecule - 1 ( pecam - 1 or cd31 ) + areas. ole also seems effective in the prevention of melanoma growth and metastasis. in an in vivo b16f10 ( mouse melanoma cell line ) allograft model of high - fat diet ( hfd ) - induced melanoma progression in c57bl / 6n mice, hfd containing 0. 02 % and 0. 04 % ole reduced hfd - driven tumor growth and lymph node metastasis, with a mechanism involving ( i ) inhibition of cell proliferation, as indicated by the reduction in the percentage of cells positive for proliferation markers ki67, cyclin d1, and cyclin - dependent kinase 4 ( cdk4 ) cells, ( ii ) suppression of angiogenesis ( reduction in cd31, ve - cadherin expression, vegf - a, vegf - c, vegf - d, vegf receptor 2 - vegfr2 - and vegfr3 ), and ( iii ) inhibition of lymphangiogenesis, as proved by staining for lymphatic vessel endothelial hyaluronan receptor ( lyve - 1 ). according to further in vitro experimental assays, ole anti - angiogenetic and lymphangiogenetic action relies on the inhibition of lipid and m2 - macrophage accumulation. in vitro results for ole are conflicting. incubation of human amelanotic melanoma cell line c32 with 100 μm, 400 μm, and 1000 μm ole for 72 h promoted cell viability. on the contrary, incubation of human melanoma cell lines a375, wm266 - 4, and m21 with 250 μm, 500 μm, and 800 μm ole for 72 h produced a dose - dependent decrease in cell viability. as deepened in a375 cells, an increase in ole effectiveness with time may be detected. ole induced inhibition of cell viability after 24 h at a concentration of 800 μm, whereas after 48 and 72 h, a decrease in the percentage of viable cells became significant with a concentration as low as 250 μm. after 48 h treatment, 500 μm ole increased the rate of apoptosis in a375 cells. in addition, 24 h incubation with 250 μm ole was sufficient to reduce invasiveness of a375 cells, while 48 h incubation with the same ole concentration reduced the phosphorylation of pro - survival kinase akt. as regards in vitro evidence for ht, the effects on cell growth seem to be cell line - dependent. treatment of c32 cells with 100 μm ht for 72 h increased cell viability, which was instead reduced by incubation with 400 μm and 1000 μm ht. incubation of human melanoma cell line a375 with 100 μm and 200 μm ht significantly diminished cell viability after 48 h. on the contrary, 48 h treatment of melanoma cell line mnt1 with 100 μm and 200 μm ht had no significant effect on cell viability. the authors attributed this dissimilarity between the mentioned cell lines to differences in the active metabolic pathways. expression analysis revealed a significant transcriptional upregulation of lactate dehydrogenase b ( ldhb ) and ldhc ( accounting for lactate conversion into pyruvate ) and glutamine synthetase ( glul ) in mnt1 cells in comparison with the a375 cell line, while sodium - coupled neutral amino acid transporter 1 ( snat1 ) and snat2 ( involved in glutamine transport within the cell ), monocarboxylate transporter 4 ( mct4, accounting for lactate export ), glyco lytic enzyme glucose - 6 - phosphate dehydrogenase ( g6pd ), and excitatory amino acid transporter 3 ( eeat3 ) were downregulated in mnt1 cells vs. a375. in a further report, treatment of human melanoma cell lines a375, ht - 144, and m74 with 50 – 250 μm ht produced a dose - and time - dependent decrease in cell viability after 24, 48, and 72 h. a detailed analysis on a375 cells ( treated with 250 μm, 375 μm, and 500 μm ht ) and ht - 144 cells ( incubated with 250 μm, 350 μm, and 450 μm ht ) performed for 24 and 48 h revealed an increase in the rate of apoptosis in both cell lines, with a dose - and time - dependent increase in tumor suppressor p53 and reduction in growth - promoting kinase akt protein levels. the activation of apoptosis pathway was further confirmed by an increase in apoptosis markers pro - activated and cleaved ( activated ) forms of caspase - 3, a dose - and time - dependent increase in cleavage ( activation ) of poly adp - ribose polymerase 1 ( parp - 1 ), and a dose - dependent increase in the phosphorylation of histone h2ax ( γh2ax ). ht - mediated induction of apoptosis was related to ros accumulation in both cell lines at the indicated ht concentrations, which was detected after 24 and 48 h. thyroid cancer is a category of neoplastic lesions with a highly variable degree of aggressiveness, arising from parafollicular c cells ( resulting in medullary thyroid cancers ) and follicular thyroid cells ( producing follicular thyroid cancer, papillary thyroid cancer, poorly differentiated thyroid cancer, hurthle cell cancers, and anaplastic thyroid cancer ). in vitro, treatment of human papillary thyroid carcinoma cell line tpc - 1 and poorly differentiated thyroid gland carcinoma cell line bcpap with 50 – 100 μm ole for 48 h produced a significant reduction in cell viability attributable to s phase and g2 / m phase cell cycle block, respectively. in both cell lines, 50 – 100 μm ole exerted an antioxidant activity against hydrogen peroxide ( h2o2 ) - induced perturbation of ros homeostasis. also, 100 μm ole caused a short - lasting ( 30 to 60 min ) reduction in phosphorylated forms pro - survival kinases erk ( phospho - erk ) and akt ( phospho - akt ) in tpc - 1 and bcpap cells. incubation of papillary thyroid cancer cell lines tpc - 1 and fb - 2 with 324 – 973 μm ht decreased cell viability after 24 and 48 h in a dose - dependent manner. a stronger action was exerted on follicular thyroid cancer cell line wro, whose cell viability was reduced even at lower doses of ht after 24 h ( 162 μm ) and 48 h ( 65 μm ) treatment. after 24 h incubation, 324 μm ht elicited an increase in the percentage of apoptotic and necrotic cells in all the three mentioned cell lines ( with a concomitant downregulation of pro - proliferative cyclin d1 and upregulation of tumor suppressor p21 at both mrna and protein levels ), increased protein level of tumor suppressor p53, and activated the intrinsic pathway of apoptosis, as corroborated by the increase in cleaved parp and cleaved caspase - 3 levels, bcl - 2 - associated agonist of cell death ( bad ) and caspase - 9 protein levels, and the release of mitochondrial cytochrome c. currently, lung cancer represents the most commonly diag nosed cancer and the main cause of cancer - related deaths worldwide, including small cell carcinoma and more common non - small cell carcinoma.