Ionized Angelica polysaccharides derivatives slow tumor growth in vivo and induce the apoptosis of HepG2 cells via mitochondria death receptor-mediated pathways in vitro
Ionized, phosphorylated (ASP P) and cationised (ASP N) derivatives of Angelica sinensis polysaccharide (ASP) were evaluated for their antitumour activity. We performed the CCK-8 assay, flow cytometry, scratch healing assay and fluorescence staining assay to detect the effects of different chemical modifications of ASP on the antitumour activity of HepG2 and Huh7 cells. Western blot was performed to detect the mechanism of antitumour effect. The results showed that ASP-P and ASP-N with maximum test concentration (240 μg·mL −1 ) had strong inhibitory effects on HepG2 cells with inhibition rates of 52.36 % and 31.76 %, respectively. Both ASP-P and ASP-N all significantly inhibited the proliferation and migration of HepG2 and Huh7 cells. Furthermore, the study revealed that both ASP-P and ASP-N up-regulated apoptosis related proteins, such as Caspase-3, Caspase-9, cleaved-caspase 9, Apaf-1, Bid, Bax, Caspase-8, FADD, Fas and down-regulated the expression of Bcl-2 to induce apoptosis in HepG2 and Huh7 cells. This observation was further corroborated by the identification of cell-cycle arrest-associated proteins CDK4, p53 and p21, where the expression of CDK4 was down-regulated, and the expression of p53 and p21 were up-regulated. Overall, ASP-P and ASP-N inhibits proliferation and migration and induces apoptosis of HepG2 and Huh7 cells by regulating the mitochondrial apoptotic pathway to achieve antitumor activity. ASP-P and ASP-N solution was injected by subcutaneous in the nude mice bearing tumors. In comparison with the control group, ASP-P and ASP-N were found to retard tumor growth to a significant extent without exerting any influence on the body weights of mice. The ASP-N group demonstrated the most favorable outcomes, exhibiting the lowest tumor volume.
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