Epigallocatechin gallate inhibits the proliferation of colorectal cancer cells by regulating Notch signaling

Heiying Jin,^1,* Wei Gong,^2,* Chunxia Zhang,^1,* Shuiming Wang<sup>1

1</sup>National Center of Colorectal Surgery, the Third Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, People’s Republic of China; ²Department of Surgery, Jiangyin Hospital of Traditional Chinese Medicine, Jiangsu, People's Republic of China

^*These authors contributed equally to this work

Aims: To explore the inhibitory effects of epigallocatechin gallate (EGCG) on the proliferation of colorectal cancer cells and on the gene expression of Notch signaling.
Methods: The colorectal cancer cells and orthotopic colorectal cancer transplant model were treated with EGCG, and MTT assay was used to test the inhibitory role of EGCG in the proliferation of colorectal cancer cells.
Results: MTT assay indicated that EGCG inhibited the proliferation of these four cell lines when the time and concentration increased, and EGCG enhanced the apoptotic rate of these four cell lines. The dosage was positively correlated to the apoptotic rate, and EGCG inhibited the proliferation of colorectal cancer cells by influencing cell cycle. In-vivo study suggested that on the seventh day, the volume of tumors reduced after administrating with 5, 10 and 20 mg/kg of EGCG. At the twenty-eighth day, the volume of tumors was significantly different in three EGCG treatment groups as compared to the control group (P < 0.05), and TUNEL assay indicated that the apoptosis of cancer cells in EGCG treated groups was markedly higher than that in the control group (P < 0.05). In these cell lines, the expressions of HES1 and Notch2 in EGCG treated groups were remarkably lower than that in the control group (P < 0.05). The expression of JAG1 decreased in SW480 cells (P = 0.019), HT-29 cells and HCT-8 cells, but increased in LoVo cells at mRNA level. The expression of Notch1 was upregulated in these four cell lines, but its expression was significantly upregulated only in LoVo and SW480 cells (P < 0.05).
Conclusion: In-vitro and in-vivo studies showed that EGCG inhibited the proliferation, induced the apoptosis and affected the cell cycle of colorectal cancer cells. After treating with EGCG, the expressions of HES1 and Notch2 was obviously inhibited, this indicated that EGCG inhibited colorectal cancer by inhibiting HES1 and Notch2.

Keywords: EGCG; Colorectal cancer cells; Cell apoptosis; Cell cycle; Notch signaling