Reference - Detail
| RRC ID | 47984 |
|---|---|
| Author | Satoh R, Hagihara K, Matsuura K, Manse Y, Kita A, Kunoh T, Masuko T, Moriyama M, Moriyama H, Tanabe G, Muraoka O, Sugiura R. |
| Title | Identification of ACA-28, a 1'-acetoxychavicol acetate analogue compound, as a novel modulator of ERK MAPK signaling, which preferentially kills human melanoma cells. |
| Journal | Genes Cells |
| Abstract |
The extracellular signal-regulated kinase (ERK) signaling pathway is essential for cell proliferation and is frequently deregulated in human tumors such as melanoma. Melanoma remains incurable despite the use of conventional chemotherapy; consequently, development of new therapeutic agents for melanoma is highly desirable. Here, we carried out a chemical genetic screen using a fission yeast phenotypic assay and showed that ACA-28, a synthetic derivative of 1'-acetoxychavicol acetate (ACA), which is a natural ginger compound, effectively inhibited the growth of melanoma cancer cells wherein ERK MAPK signaling is hyperactivated due to mutations in the upstream activating regulators. ACA-28 more potently inhibited the growth of melanoma cells than did the parental compound ACA. Importantly, the growth of normal human epidermal melanocytes (NHEM) was less affected by ACA-28 at the same 50% inhibitory concentration. In addition, ACA-28 specifically induced apoptosis in NIH/3T3 cells which were oncogenically transformed with human epidermal growth factor receptor-2 (HER2/ErbB2), but not in the parental cells. Notably, the ACA-28-induced apoptosis in melanoma and HER2-transformed cells was abrogated when ERK activation was blocked with a specific MEK inhibitor U0126. Consistently, ACA-28 more strongly stimulated ERK phosphorylation in melanoma cells, as compared in NHEM. ACA-28 might serve as a promising seed compound for melanoma treatment. |
| Volume | 22(7) |
| Pages | 608-618 |
| Published | 2017-7-1 |
| DOI | 10.1111/gtc.12499 |
| PMID | 28485554 |
| MeSH | 3T3 Cells Animals Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology* Apoptosis / drug effects Benzyl Alcohols / chemistry Benzyl Alcohols / pharmacology* Butadienes / pharmacology Cell Line, Tumor Cell Transformation, Neoplastic / drug effects Cell Transformation, Neoplastic / pathology Enzyme Inhibitors / pharmacology Extracellular Signal-Regulated MAP Kinases / metabolism Gene Expression Regulation, Enzymologic / drug effects Humans MAP Kinase Kinase 1 / antagonists & inhibitors Melanocytes / cytology Melanocytes / drug effects Melanocytes / metabolism Melanoma / drug therapy* Melanoma / metabolism Melanoma / pathology Mice Nitriles / pharmacology Phosphorylation / drug effects Signal Transduction / drug effects |
| IF | 1.655 |
| Times Cited | 6 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 3 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Yeast | S. pombe strains |