title: MK615, a Prunus mume Steb. Et Zucc ('Ume') extract, attenuates the growth of A375 melanoma cells by inhibiting the ERK1/2-Id-1 pathway.
abstract: The Japanese apricot, a commonly consumed food called 'Ume' in Japan, has been used for a traditional Japanese medicine for centuries. MK615, an extract of compounds from 'Ume', has strong antitumorigenic and antiinflammatory effects including the induction of apoptosis and autophagy, and inhibition of cytokine production mediated via the inhibition of MAPKs signaling including ERK-1/2, JNK and p38MAPK. The inhibitor of DNA binding 1 (Id-1), a basic helix-loop-helix (bHLH) transcription factor family, is essential for DNA binding and the transcriptional regulation of various proteins that play important roles in the development, progression and invasion of tumors. In melanoma, Id-1 is constitutively expressed in the late and early stages, suggesting it as a therapeutic target in patients with melanoma. This study reports that MK615 profoundly reduced both the mRNA- and protein expression levels of Id-1 and inhibited cell growth in A375 melanoma cells. MK615 markedly inhibited the phosphorylation of ERK1/2, which is associated with Id-1 protein expression in A375 cells. Id-1-specific RNAi induced the death of A375 cells. Moreover, the expression of Bcl-2 was decreased by both MK615 and Id-1-specific RNAi in A375 cells. The results suggest that MK615 is a potential therapeutic agent for treating malignant melanoma.
authors.affiliation: Department of Dermatology, Cardiovascular and Respiratory Disorders Advanced Therapeutics, Kagoshima University, Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
authors.forename: Ko-ichi
authors.initials: K
authors.lastname: Tada
authors.forename: Ko-ichi
authors.initials: K
authors.lastname: Kawahara
authors.forename: Shigeto
authors.initials: S
authors.lastname: Matsushita
authors.forename: Teruto
authors.initials: T
authors.lastname: Hashiguchi
authors.forename: Ikuro
authors.initials: I
authors.lastname: Maruyama
authors.forename: Takuro
authors.initials: T
authors.lastname: Kanekura
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis; D016923:Cell Death; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D027861:Prunus / Q000737:chemistry*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; C517469:MK615 extract; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D048051:p38 Mitogen-Activated Protein Kinases