title: TRPA1 is functionally expressed in melanoma cells but is not critical for impaired proliferation caused by allyl isothiocyanate or cinnamaldehyde.
abstract: Melanoma is the most dangerous form of skin cancer occurring in Caucasians with rising incidence. They are remarkably resistant to conventional anti-tumour therapies like chemotherapy and radiotherapy. Therefore, new treatment strategies are urgently needed. Anti-tumour effects of phytochemicals such as allyl isothiocyanate or cinnamaldehyde have been demonstrated in various melanoma models in vitro and in vivo. Considering their high potency as transient receptor potential A1 (TRPA1)-activating compounds, we examined the functional expression of TRPA1 channels in different melanoma cell lines as well as in non-malignantly transformed primary melanocytes. The presence of TRPA1 transcripts could be detected in most of the melanoma cell lines. Furthermore, single-cell calcium imaging and patch clamp electrophysiology confirmed the presence of functional TRPA1 channels in those cell lines. Proliferation assays revealed that allyl isothiocyanate and cinnamaldehyde clearly reduce the proliferation of melanoma cells, but this effect is independent of an activation of TRPA1 channels, making it unlikely that ionic currents through TRPA1 are responsible for the anti-tumour effects of mustard oil and cinnamaldehyde.
authors.affiliation: Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Härtelstrasse 16-18, Leipzig, Germany.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Oehler
authors.forename: Anja
authors.initials: A
authors.lastname: Scholze
authors.forename: Michael
authors.initials: M
authors.lastname: Schaefer
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hill
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000171:Acrolein / Q000031:analogs & derivatives / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology; D008544:Melanocytes / Q000502:physiology; D008545:Melanoma / Q000378:metabolism* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011687:Purines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012430:Ruthenium Red / Q000494:pharmacology; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D000970:Antineoplastic Agents; D015220:Calcium Channels; D017879:Isothiocyanates; D009419:Nerve Tissue Proteins; D011687:Purines; D012333:RNA, Messenger; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels; D012430:Ruthenium Red; D000171:Acrolein; C004471:allyl isothiocyanate; C012843:cinnamaldehyde; D002118:Calcium