Asparagus Polysaccharide Suppresses the Migration, Invasion, and Angiogenesis of Hepatocellular Carcinoma Cells Partly by Targeting the HIF-1α/VEGF Signalling Pathway In Vitro

Abstract

Hypoxia-inducible factor-1α (HIF-1α) plays a key role by triggering the transcriptional activation of a number of genes involved in migration, invasion, and angiogenesis in hepatocellular carcinoma (HCC). Thus, suppressing tumour growth by targeting the HIF-1α/VEGF signalling pathway represents a promising strategy for the treatment of HCC. In our previous studies, we found that asparagus polysaccharide (ASP) suppressed the proliferation and promoted the apoptosis of HCC cells both in vivo and in vitro. To further explore the potential mechanisms of the antitumor effects of ASP in HCC, we investigated effects of ASP on the migration, invasion, and angiogenesis of HCC cells (SK-Hep1 and Hep-3B) using an in vitro experimental model. First, we found that ASP effectively suppressed the proliferation of the SK-Hep1 and Hep-3B cells but did not cause significant cytotoxicity in normal liver cells (L-O2). Then, we found that ASP inhibited the migration and invasion of the SK-Hep1 and Hep-3B cells and HCC cells-induced angiogenesis of human umbilical vein endothelial cells in a concentration-dependent manner. Mechanistic studies revealed that the inhibition of migration, invasion, and angiogenesis by ASP in the SK-Hep1 and Hep-3B cells might occur via the downregulation of HIF-1α/VEGF signalling pathway. Finally, our results also showed that the inhibition of HIF-1α by ASP may be mediated through the downregulation of the phosphorylation levels of AKT, mTOR, and ERK. In conclusion, our results suggest that ASP suppresses the migration, invasion, and angiogenesis of HCC cells partly via inhibiting the HIF-1α/VEGF signalling pathway.

Engineering Exosome-Like Nanovesicles Derived from Asparagus cochinchinensis Can Inhibit the Proliferation of Hepatocellular Carcinoma Cells with Better Safety Profile

“…Similar results were reported that Asparagus polysaccharide can induce approximately 80% growth inhibition of HCC cells in comparison to 20% inhibition of LO 2 cells. 14 Hep G2 cell is one of the most widely used cells in the anti-tumor evaluation of Asparagus extracts. 16 , 26 To obtain more information for comparison, Hep G2 cell line was selected for the subsequent experiments.…”

“…Besides, A. cochinchinensis has multiple pharmacological properties, including anticancer, antioxidation, antifungal, and antiaging activities. [14][15][16][17][18][19] However, the effector mechanism remains partially understood. In this study, A. Cochinchinensis-derived nanovesicles (ACNVs) were isolated, and the antiproliferative activity and apoptosis-inducing mechanism against hepatocellular carcinoma (HCC) were investigated.…”

Ayurveda botanicals in COVID-19 management: An in silico multi-target approach

“…The connection of hypoxia and inflammatory signals is well established throughHIF1α gene [ 81 ]. Asparagus polysaccharides potentially inhibited HIF1α signalling which might ameliorate fatal systemic inflammation [ 82 ]. TC also exhibited anti-inflammatory effects in systemic models significantly [ 83 ].…”

Ayurveda botanicals in COVID-19 management: An in silico- multitarget approach

“…WS showed prophylactic effect in pulmonary hypertension characterised by hypoxia and in ammation 64 . The connection of hypoxia and in ammatory signals is well established throughHIF1α gene 65 .Asparagus polysaccharides potentially inhibited HIF1α signalling which might ameliorate fatal systemic in ammation 66 . TC also exhibited anti-in ammatory effects in systemic models signi cantly 67 .…”