Pseudostellaria heterophylla Extract Polysaccharide H-1-2 Suppresses Pancreatic Cancer by Inhibiting Hypoxia-Induced AG2

Abstract

We aimed to examine the therapeutic potential of polysaccharide H-1-2, a bioactive component of Pseudostellaria heterophylla, against pancreatic cancer, as well as to demonstrate the underlying molecular mechanisms. Invasion and migration of pancreatic cells treated with H-1-2 were evaluated. A xenograft tumor mouse model was established to assess the effect of H-1-2 on tumor growth. Expression levels of hypoxic inducible factor-1a (HIF1a) and anterior gradient 2 (AGR2) were measured in pancreatic cells after H-1-2 treatment. Luciferase report and chromatin immunoprecipitation assays were conducted to investigate HIF1a regulation on AGR2. AGR2 expression was re-introduced into pancreatic cells to assess the role of AGR2 as a downstream effector of hypoxia after H-1-2 treatment. H-1-2 inhibited invasion and migration of pancreatic cancer cells, repressed xenograft pancreatic tumor growth, and increased survival of mice. H-1-2 repressed AGR2 expression in pancreatic cancer cells through the hypoxia response element (HRE) in its promoter region. Ectopic AGR2 expression partially negated the H-1-2 inhibitory effect on invasion and migration of pancreatic cells and on xenograft pancreatic tumors growth, and it also compromised the H-1-2 promotional effect on survival of mice. We conclude that H-1-2 suppresses pancreatic cancer by inhibiting hypoxia-induced AGR2 expression, supporting further investigation into its efficacy against pancreatic cancer in clinical settings.

Comparative chemical characters of Pseudostellaria heterophylla from geographical origins of China

“…The report showed that the purified polysaccharide has anti-inflammatory activity through activating the TLR4 signal pathways and decreasing the level of IL-1β and TNF-α ( You et al, 2021 ). Sun et al (2020) found that H-1–2 which is the purified polysaccharide in P. heterophylla has the inhibitory effect on pancreatic cancer. Meanwhile, polysaccharide in P. heterophylla has the effect of lowering blood sugar by stimulating insulin secretion level ( Chen et al, 2018 ).…”

Polysaccharide H-1-2 Ameliorates High Glucose-Induced Podocyte Dysfunction by Suppressing Epithelial-to-Mesenchymal Transition via Restoration of SIRT1 <i>in Vivo</i> and <i>in Vitro</i>

“…for diabetic nephropathy. H-1-2 is a novel polysaccharide of Pseudostellaria heterophylla, which has been reported to exert anti-hyperglycemic and anti-cancer effects in recent studies (Fang et al 2018, Sun et al 2020. Herein, we investigated whether H-1-2 ameliorates HG induced-podocyte depletion and EMT in vivo and ex vivo, and preliminarily uncovered the underlying mechanism.…”

Antitumor Activity of Pulvomycin via Targeting Activated-STAT3 Signaling in Docetaxel-Resistant Triple-Negative Breast Cancer Cells

“…MDA-MB-231 or MDA-MB-231-DTR cells were injected subcutaneously into the flanks of mice (4 × 10 6 cells in 200 µL PBS), and tumors were allowed to grow for 10 days until tumor volume reached approximately 100 mm 3 . The mice were randomized into vehicle control and treatment groups ( n = 6) [ 30 ]. Vehicle control (normal saline with 0.5% ( w / v ) Tween 80), docetaxel (10 mg/kg body weight), pulvomycin (10 mg/kg body weight), or a combination of docetaxel (10 mg/kg body weight) and pulvomycin (10 mg/kg body weight) was administered intraperitoneally (i.p.)…”