論文 - 詳細
| RRC ID | 63117 |
|---|---|
| 著者 | Kamimura M, Sasaki A, Watanabe S, Tanaka S, Fukukawa A, Takeda K, Nakamura Y, Nakamura T, Kuramochi K, Otani Y, Hashimoto F, Ishimaru K, Matsuo T, Okamoto S. |
| タイトル | Chemical and molecular bases of dome formation in human colorectal cancer cells mediated by sulphur compounds from Cucumis melo var. conomon. |
| ジャーナル | FEBS Open Bio |
| Abstract |
Colorectal cancer was the third most commonly diagnosed malignant tumor and the fourth leading cause of cancer deaths worldwide in 2012. A human colorectal cancer cell line, RCM-1, was established from a colon cancer tissue diagnosed as a well-differentiated rectum adenocarcinoma. RCM-1 cells spontaneously form 'domes' (formerly designated 'ducts') resembling villiform structures. Two sulphur-containing compounds from Cucumis melo var. conomon (Katsura-uri, or Japanese pickling melon), referred to as 3-methylthiopropionic acid ethyl ester (MTPE) and methylthioacetic acid ethyl ester (MTAE), can induce the differentiation of the unorganized cell mass of an RCM-1 human colorectal cancer cell culture into a dome. However, the underlying molecular mechanisms of such dome formation have not been previously reported. Here, we performed a structure-activity relationship analysis, which indicated that methylthioacetic acid (MTA) was the lowest molecular weight compound with the most potent dome-inducing activity among 37 MTPE and MTAE analogues, and the methylthio group was essential for this activity. According to our microarray analysis, MTA resulted in down-regulation of 537 genes and up-regulation of 117 genes. Furthermore, MTA caused down-regulation of many genes involved in cell-cycle control, with the cyclin E2 (CCNE2) and cell division cycle 25A (CDC25A) genes being the most significantly reduced. Pharmacological analysis showed that the administration of two cell-cycle inhibitors for inactivating CDC25A phosphatase (NSC95397) and the cyclin E2/cyclin-dependent kinase 2 complex (purvalanol A) increased the dome number independently of MTA. Altogether, our results indicate that MTA is the minimum unit required to induce dome formation, with the down-regulation of CDC25A and possibly CCNE2 being important steps in this process. |
| 巻・号 | 10(12) |
| ページ | 2640-2655 |
| 公開日 | 2020-12-1 |
| DOI | 10.1002/2211-5463.13001 |
| PMID | 33048473 |
| PMC | PMC7714076 |
| MeSH | Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology* Cell Differentiation / drug effects Colorectal Neoplasms / drug therapy* Colorectal Neoplasms / metabolism Colorectal Neoplasms / pathology Cucumis melo / chemistry* Drug Screening Assays, Antitumor Esters / chemistry Esters / pharmacology Humans Propionates / chemistry Propionates / pharmacology Sulfur Compounds / chemistry Sulfur Compounds / pharmacology* Tumor Cells, Cultured |
| IF | 2.231 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Ehrlich(RCB0142) |