A Novel Caffeoylquinic Acid from Lonicera japonica Exerts Cytotoxic Activity by Blocking the YAP-CTGF Signaling Pathway in Hepatocellular Carcinoma

• Published in: Revista brasileira de farmacognosia Vol. 33; no. 4; pp. 736 - 746
• Main Authors: Shen, Wanying, Wei, Xiaofang, Li, Yangfang, Liu, Chenxiao, Ge, Lanlan, Yao, Jie, Zeng, Xiaobin, Tang, Xudong
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-08-2023
• Subjects: Medicine; Original Article; Pharmacy; The Hippo signaling pathway; New drug; Primary liver cancers; The Wnt signaling pathway; Chinese herbal medicines
• ISSN: 1981-528X; 1981-528X
• DOI: 10.1007/s43450-023-00397-4

We have purified a novel caffeoylquinic acid named 3,4-di-
O
-caffeoylquinic acid isobutyl ester from the flower buds of
Lonicera japonica
Thunb., Caprifoliaceae. However, the biological function of 3,4-di-
O
-caffeoylquinic acid isobutyl ester is still unknown. Here, we found that 3,4-di-
O
-caffeoylquinic acid isobutyl ester effectively inhibited the proliferation and migration of hepatocellular carcinoma cells, and it displayed less toxicity to a normal liver cell line. Mechanistic studies showed that 3,4-di-
O
-caffeoylquinic acid isobutyl ester diminished the expression of YAP at the mRNA level. Overexpression of YAP significantly rescued HepG2 cells from the 3,4-di-
O
-caffeoylquinic acid isobutyl ester–induced suppression of proliferation and migration. Furthermore, the YAP downstream target gene CTGF was significantly repressed upon 3,4-di-
O
-caffeoylquinic acid isobutyl ester treatment, which was ameliorated by YAP overexpression. In addition, 3,4-di-
O
-caffeoylquinic acid isobutyl ester decreased the expression of β-catenin as well as CDK4/6. Collectively, 3,4-di-
O
-caffeoylquinic acid isobutyl ester exerts antihepatocellular carcinoma activity by inhibiting the YAP-CTGF pathway which controls the proliferation and migration of hepatocellular carcinoma cells. The Wnt/β-catenin pathway might be another pathway by which 3,4-di-
O
-caffeoylquinic acid isobutyl ester exerts antihepatocellular carcinoma activity. As a novel natural compound, 3,4-di-
O
-caffeoylquinic acid isobutyl ester might be a promising agent for hepatocellular carcinoma therapy.
Graphical Abstract