烏龍茶成分Theasinensin A可透過調降MMP-9與CCL2抑制12-0-Tetradecanoylphorbol-13-acetate所誘導HT-29腸癌細胞株之轉移活性

Theasinensin A Exerts Anti-metastatic Effects on HT-29 Cells via Downregulating the Expression of MMP-9 and CCL2

李佳軒(Chia-Hsuan Lee) ； 林偉盛(Wei-Sheng Lin) ； 楊美珠(Mei-Chu Yang) ； 何其儻(Chi-Tang Ho) ； 潘敏雄(Min-Hsiung Pan)

《臺灣農業化學與食品科學》 58卷4&5期 (2020/10) Pp. 127-137

https://doi.org/10.6578/TJACFS.202010_58(4_5).0004

摘要

癌症長年位居我國十大死因之首，亦是許多已開發國家主要死因，而在所有癌症中結腸直腸癌死亡率高居第二，由於結腸直腸癌在初期階段病症不易察覺，因此當診斷並開始接受治療時，大腸癌患者其病程都已進入轉移階段，此時已很難根除，因此大腸癌患者死亡的主因為癌症轉移（cancer metastasis）而非腫瘤本身。Theasinensin A是烏龍茶中主要的聚酯型兒茶素，為EGCG之二聚體。研究已經指出Theasinensin A具有抗氧化、抗發炎、誘發癌細胞凋亡等生物活性。本研究初步透過明膠蛋白酵素電泳法分析發現Theasinensin A可能具有抑制腸癌細胞轉移的潛力，後續進一步探討Theasinensin A是否具抑制12-O-Tetradecanoylphorbol-13-acetate（TPA）誘導腸癌細胞HT-29轉移之能力與相關分子機制。MMP-9與CCL2兩者對於腸癌轉移的內滲（intravasation）與外滲（extravasation）階段扮演重要角色，本研究以兩者之表達作為腸癌細胞轉移之目標蛋白。結果顯示，Theasinensin A可以有效的抑制由TPA所誘導之上皮-間質細胞轉換（epithelial to mesenchymal transition, EMT）、間質－上皮細胞轉換 （mesenchymal to epithelial transition, MET）及細胞的非貼覆性生長。此外，Theasinensin A可能透過抑制TPA所誘導的ERK1/2和p38之磷酸化以及AP-1的活性進而抑制MMP-9和CCL2的蛋白表現量從而有效地抑制由TPA所誘導的腸癌細胞轉移。綜上所述，Theasinensin A可能具有抑制腸癌細胞轉移之潛力。

關鍵字

癌症轉移 ； 聚酯型兒茶素A ； 基質金屬蛋白酶9 ； 趨化素配體2

並列摘要

Cancer metastasis, the terminal stage of cancer development, is accounting for approximately 90% of all human cancer mortalities. Previous research has suggested that theasinensin A (TSA) has anti-inflammatory effects; however, its potential for inhibiting colon cancer metastasis remains to be unclear. Therefore, in this research, we focused on investigating the mechanism of inhibitory effects of TSA on TPA-induced colon cancer cell migration. Previous studies show that matrix metalloproteinase-9 (MMP-9) and C-C motif ligand 2 (CCL2) are critical factors that cause cancer cell intravasation and extravasation. In our research, we tried to figure out if TSA can downregulate TPA-induced protein expression and activity of MMP-9 and CCL2 mRNA expression in human colon HT-29 cells. Our results showed that TSA effectively inhibited TPA-induced epithelial-mesenchymal transition (EMT), mesenchymal-epithelial transition (MET), cell anchorage-eindependent growth, and cell migration in HT-29 cells. Moreover, TSA may downregulate TPA-induced expression of MMP-9 and CCL2 via inhibiting TPA-induced phosphorylation of ERK1/2 and p38 and AP-1 activation whereby further inhibit cancer cell migration. Our findings suggested that TSA could be a potential compound for preventing colon cancer metastasis.

並列關鍵字

Cancer metastasis ； theasinensin A (TSA) ； matrix metalloproteinase-9 (MMP-9) ； C-C motif ligand 2 (CCL2)