A derivant of ginsenoside CK and its inhibitory effect on hepatocellular carcinoma
Jingjing Zhang, Yangliu Tong, Xun Lu, Fangming Dong, Xiaoxuan Ma, Shiyu Yin, Ying He, Yonghong Liu, Qingchao Liu, Daidi Fan
Abstract
Epidemiological studies have shown that hepatocellular carcinoma (HCC) is a main cause of tumor death worldwide. Accumulating data indicate that ginsenoside CK is an effective compound for preventing HCC growth and development. However, improvement of pharmaceutical effect of the ginsenoside CK is still needed. In our study, we performed acetylation of ginsenoside CK (CK-3) and investigated the antitumor effects of the derivative in vitro and in vivo. The cytotoxicity analysis revealed that compared with CK, CK-3 could inhibit the proliferation of multiple tumor cell lines at a lower concentration. Treating with CK-3 on HCC cells arrested cell cycle in G2/M phase and induced cell apoptosis through AO/EB staining, TUNEL analysis and flow cytometry. Meanwhile, CK-3 significantly inhibited tumor growth in an HCC xenograft model and showed no side effect on the function of the main organs. Mechanistically, whole transcriptome analysis revealed that the antitumor effect of CK-3 was involved in the Hippo signaling pathway. The immunoblotting and immunofluorescence results illustrated that CK-3 directly facilitated the phosphorylation of YAP1 and decreased the expression of the main transcription factor TEAD2 in HCC cell lines and tumor tissue sections. Collectively, our results demostrate the formation of a new derivative of ginsenoside CK and its regulatory mechanism in HCC, which could activate the Hippo-YAP1-TEAD2 signaling pathway to regulate HCC progression. This research could provide a new direction for traditional Chinese medicine in the therapy of tumors.