Pachymic Acid Inhibits Growth and Metastatic Potential in Liver Cancer HepG2 and Huh7 Cells

• Published in: Biological & pharmaceutical bulletin 2023/01/01, Vol.46(1), pp.35-41
• Main Authors: Jiang, Feng, Zhu, Tieming, Yang, Chunfeng, Chen, Yang, Fu, Zhidong, Jiang, Lihui, Liu, Yongzhi
• Format: Article
• Language: English
• Subjects: Acids; Apoptosis; Caspase-3; Caspase-9; Cell growth; Cell Line, Tumor; Cell migration; Cytochrome c; Diuretics; Epithelial-Mesenchymal Transition; epithelial-to-mesenchymal transition (EMT); Gelatinase A; Hepatocytes; Humans; Inflammation; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; Matrix metalloproteinase; Matrix Metalloproteinase 2 - genetics; Mesenchyme; Metalloproteinase; Metastases; Metastasis; Oxidants; pachymic acid
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b22-00440

Pachymic acid (PA), exacted from Polyporaceae, has been known for its biological activities including diuretic, dormitive, anti-oxidant, anti-aging, anti-inflammatory and anticancer properties in several types of diseases. Recently, studies have demonstrated that PA could suppress cell growth and induce cell apoptosis in different kinds of cancer cells. But the underlying mechanisms remain poorly elucidated. In the current study, we investigated the effect of pachymic acid on liver cancer cells and its underlying mechanisms. Our results evidenced that pachymic acid effectively inhibited the cell growth and metastatic potential in HepG2 and Huh7 cells. Mechanistically, we revealed that pachymic acid triggered cell apoptosis by increasing caspase 3 and caspase 9 cleavage, upregulating Bax and cytochrome c expression, while reducing the expression of Bcl2. Besides, pachymic acid could markedly inhibit the cell invasion and migration and cell metastatic potential by mediating epithelial-to-mesenchymal transition (EMT) markers and metastasis-associated genes in HepG2 and Huh7 cells. In addition, we demonstrated that FAK-Src-Jun N-terminal kinase (JNK)-matrix metalloproteinase 2 (MMP2) axis was involved in PA-inhibited liver cell EMT. Together, these results contribute to our deeper understanding of the anti-cancer effects of pachymic acid on liver cancer cells. This study also provided compelling evidence that PA might be a potential therapeutic agent for liver cancer treatment.