latanoprost and Skin-Neoplasms

To determine if there is an association between the use of latanoprost ophthalmic solution and malignant melanoma and to assess the evidence of a plausible biological mechanism.. Two safety databases were reviewed: one representing all latanoprost (n=24) and fixed-combination latanoprost/timolol (n=16) clinical trials conducted from November 1992 through November 2007 and a global safety database of all spontaneous non-trial-related clinical reports spanning 13 and 9 years for latanoprost and for latanoprost/timolol, respectively. A systematic PubMed search for studies evaluating potential mechanisms was conducted.. Amongst 12,880 latanoprost-treated subjects in clinical trials, no reported cases of ocular melanoma and three cases of cutaneous melanoma were identified. Of 19,940 cases recorded in the global safety database, 22 reports of ocular/cutaneous neoplasms were identified. Of these neoplasms, 11 were ocular and six were cutaneous melanomas. Possible association with latanoprost use could not be excluded in three ocular and one periorbital report. In vitro and in vivo data were consistent with a mechanism whereby the increased iris pigmentation results from stimulation of melanin synthesis by induction of tyrosinase transcription without increasing mitotic activity.. There is no evidence at present that establishes a link between latanoprost use and either ocular or cutaneous melanoma.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Child; Child, Preschool; Databases, Factual; Drug Combinations; Evidence-Based Medicine; Eye Neoplasms; Female; Humans; Latanoprost; Male; Melanoma; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Skin Neoplasms; Timolol; Young Adult

Topics: Aged, 80 and over; Antihypertensive Agents; Choroid Neoplasms; Female; Humans; Latanoprost; Melanoma; Middle Aged; Prostaglandins F, Synthetic; Skin Neoplasms

Topics: Aged; Antihypertensive Agents; Face; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Melanoma; Melanosis; Prostaglandins F, Synthetic; Skin Neoplasms; Skin Pigmentation; Skin Transplantation

The intraocular pressure-lowering drug latanoprost, a phenyl-substituted analogue of prostaglandin F2 alpha (PGF2 alpha), increases iris pigmentation in a small number of patients. In theory, this could be due to increased melanogenesis or melanocyte proliferation. To distinguish these two possibilities, the present study examined the effects of latanoprost on tyrosinase activity (the rate-limiting step for melanin synthesis) and mitotic index of cultured melanoma lines. Murine cutaneous melanoma lines (S91 and B16), and human uveal (OCM1, OCM3, and OM431) and cutaneous (SK-MEL5 and M21) melanoma lines were cultured with PGE1, PGE2, PGF2 alpha, latanoprost, or the adenylate cyclase stimulating agent forskolin. After treatment, tyrosinase was assayed with respect to its dopa oxidase activity using a colorimetric assay. PGE1, PGE2, PGF2 alpha, and latanoprost greatly increased tyrosinase activity in murine melanoma lines and caused small increases in tyrosinase activity in human uveal and cutaneous melanoma lines. Similar results were obtained with the cAMP-elevating compound forskolin. Cyclic AMP content, as determined by an enzyme-linked immunoassay, was similarly increased by all treatments, with forskolin being the most potent stimulator. Since the species difference in tyrosinase activity was observed without an apparent difference in induction of cAMP, latanoprost would appear to induce tyrosinase activity through a non-cAMP-dependent pathway. Finally, latanoprost and PGF2 alpha did not enhance the mitotic index of human uveal or cutaneous melanoma lines, measured by [6-3H] thymidine uptake, although they increased the mitotic index of one murine cutaneous line. Given that latanoprost induced tyrosinase activity, but did not increase the mitotic index in any of the human melanoma lines studied, this suggests that the in vivo iris pigmentation side effect of latanoprost may not result from increased cell division, but from elevated tyrosinase activity.

Topics: Adenylyl Cyclases; Alprostadil; Animals; Colforsin; Cyclic AMP; Dinoprost; Dinoprostone; Enzyme Induction; Enzyme-Linked Immunosorbent Assay; Humans; Intraocular Pressure; Latanoprost; Melanoma; Mice; Mitotic Index; Monophenol Monooxygenase; Pigmentation; Prostaglandins F, Synthetic; Skin Neoplasms; Stimulation, Chemical; Time Factors; Tumor Cells, Cultured; Uveal Neoplasms