Paeoniflorin suppresses pancreatic cancer cell growth by upregulating HTRA3 expression

Abstract

Paeoniflorin (PF) is an active monoterpene glycoside extracted from Paeonia lactiflora Pall. PF has exhibited antitumor effects in various cancer types. However, the effects of PF in pancreatic cancer are largely unexplored. Here, we showed that PF suppressed growth of pancreatic cancer cell lines Capan-1 and MIAPaCa-2 and profoundly sensitized these cells to X-ray irradiation. Through microarray analysis, we identified HTRA3, a tumor-suppressor candidate gene, as the most increased gene upon PF treatment in Capan-1 cells. Ectopic expression of HTRA3 led to reduced cell proliferation and increased expression of apoptotic protein Bax, suggesting a tumor suppressive role of HTRA3 in pancreatic cancer cells. Together, our results provide a set group of genetic proofs and biological proofs that PF inhibited pancreatic cancer growth by upregulating HTRA3.

Paeoniflorin: a monoterpene glycoside from plants of Paeoniaceae family with diverse anticancer activities

“…Based on studies performed in recent years, it is found Paeoniflorin combined with gemcitabine inhibits pathways EGFR/MAPK/ERK and ErbB3/PI3K/Akt, and increases proliferation of pancreatic cancer cell ErbB3 . Some other studies show that Paeoniflorin in concentration of 1000 μmol/l inhibits growth of pancreatic cancer cell through up‐regulating expression of HRTA3 and promoting HTRA3 mediated apoptosis . In 2018, Huang et al .…”

“…[46] Some other studies show that Paeoniflorin in concentration of 1000 lmol/l inhibits growth of pancreatic cancer cell through up-regulating expression of HRTA3 and promoting HTRA3 mediated apoptosis. [47] In 2018, Huang et al [48] found that Paeoniflorin inhibits proliferation of human pancreatic cancer cell Pane-1 and promotes apoptosis, for which the mechanism is probably that the pathway Caspase is activated.…”

“…Inhibit pancreatic cancer cell growth through up-regulated expression of HTRA3 and promoting HTRA3-mediated apoptosis [47] 12.5, 50, 200, 800 lmol/l Pancreatic cancer cell line panc-1…”

Analysis of Paeoniflorin Treatment of Cancer Based on Bioinformatic Network and Potential Target Prediction

“…Establishing a drug-targets-pathway network to visualize the pharmacological activity of paeoni orin. For example, breast cancer [44], colorectal cancer [45], glioma [17], pancreatic cancer [46], multi-target potential mechanisms are usually our exploration targets for cancer research. Therefore, paeoni orin may be a promising resource for use as a chemical moiety or active ingredient for future drug discovery.…”

The Anticancer Effects of Paeoniflorin and Its Underlying Mechanisms

“…36 Global analysis of gene expression showed that HTRA3 is the most increased gene upon PF treatment in Capan-1 cells; further investigation demonstrated that HTRA3 increases the expression level of Bax, thus inducing pancreatic cancer cell apoptosis. 22 A novel study revealed that by inhibiting prolactin, PF induces prolactinoma cell apoptosis through the mitochondria-dependent pathway, which is related to phosphorylated P53 upregulation. 60 Moreover, PF-induced apoptosis of A549 cells is due to activation of the Fas/Fas ligand apoptotic system, reflected in the increased expression of Fas/apoptosis-1 and its 2 ligands.…”