Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors worldwide. Studies have documented the antitumor activities of various polysaccharides derived from Antrodia cinnamomea (AC); however, to date, the antitumor activity of the oligosaccharide fragment related to galactomannan polysaccharide in AC remains unreported. In this study, we disclosed that the backbone tetrasaccharide derivative of AC galactomannan, designated as ACP-3, demonstrates specific binding to mannose receptors (MR) on the surface of Hep G2 cells, facilitating its cellular internalization. This interaction thereby elicited potent antiproliferative effects through dual mechanisms: ROS/JNK signaling-induced apoptosis and ROS-mediated autophagy-induced cell death. In vivo studies further validated the tumor-targeting capability of ACP-3, as monotherapy significantly suppresses the growth of H22 solid tumors. Notably, the co-administration of ACP-3 with cyclophosphamide (CTX) could synergistically enhance antitumor activity and concurrently alleviate CTX-induced adverse effects such as weight loss, hepatorenal toxicity, and immune dysfunction. These findings collectively establish ACP-3 as a promising therapeutic candidate for the treatment of HCC.
Yutian Zhang,Diying Li,Zhuo Wang,Wanting Zang,Pan Rao,Yunxiang Liang,Yuxia Mei
To enhance production of Antrodia cinnamomea triterpenoids (ACTs) from mycelia in solid-state culture, α-terpineol was added to the medium as an elicitor at an optimal concentration of 0.05 mL L−1. Multi-stage solvent extraction and HPLC analysis were performed, and the compositions of ACTs-E (from culture with elicitor) and ACTs-NE (from culture without elicitor) were found to be quite different. In assays of in vitro antitumor activity, ACTs-E, in comparison with ACTs-NE, produced stronger viability reduction in several tumor cell lines and stronger apoptosis induction in HeLa in a dose-dependent manner. Several related proteins involved in the mitochondrial pathway of apoptosis (p53, Bax, caspase-3) did not show expression upregulation by ACTs-E, suggesting that apoptosis induction occurred through a p53-independent process. Further analysis revealed that ACTs-E strongly inhibited synthesis of topoisomerase I (TOP1) and tyrosyl-DNA phosphodiesterase I (TDP1), which are involved in DNA repair, at both transcriptional and protein levels. Our findings suggest that ACTs-E have potential for applications in the pharmaceutical, clinical, and functional food industries, as a novel antitumor agent and a dual TOP1/TDP1 inhibitor.
危险品化学品经营许可证（带存储）