Hispidulin exhibits potent anticancer activity in�vitro and in�vivo through activating ER stress in non‑small‑cell lung cancer cells

Abstract

Hispidulin is a medicinal natural compound isolated from S. involucrata, which exhibits potent anticancer properties. However, there are few reports on its effects on lung cancer cells. Therefore, the current study investigated the effects of hispidulin on cell viability and apoptosis in human non-small-cell lung cancer (NSCLC) cell lines NCI-H460 and A549 in vitro and in vivo. Methyl thiazolyl tetrazolium, colony formation assay, Hoechst 33342 staining, flow cytometry and western blotting were performed on Human NCI-H460 and A549 cells. A mouse xenograft model was also established using NCI-H460 cells. The results showed that the growth of NCI-H460 and A549 cells was inhibited, while apoptosis was promoted by hispidulin via increased generation of reactive oxygen species (ROS) in a dose-dependent manner. Furthermore, hispidulin triggered apoptosis in NSCLC cells through upregulating the expression of cleaved caspase-3 and cleaved poly [ADP-ribose] polymerase. All these effects were reversed upon pretreatment with glutathione, a selective ROS inhibitor. In addition, endoplasmic reticulum stress (ER stress) in NCI-H460 cells was activated by hispidulin. Pretreatment with tauroursodeoxycholic acid, a specific ER stress inhibitor, effectively reduced the cell apoptosis induced by hispidulin. In conclusion, hispidulin induces ROS-mediated apoptosis via activating the ER stress pathway. The current study provides theoretical basis for the antitumor effect of hispidulin in NSCLC.

Hesperetin from Root Extract of Clerodendrum petasites S. Moore Inhibits SARS-CoV-2 Spike Protein S1 Subunit-Induced NLRP3 Inflammasome in A549 Lung Cells via Modulation of the Akt/MAPK/AP-1 Pathway

“…On the other hand, many commercially available pure compounds found in C. petasites , including hispidulin, hesperetin, and hesperidin, were acknowledged for their potent medicinal effects, such as anti-cancer and anti-inflammatory activities [ 21 , 22 , 35 ]. Briefly, hispidulin exhibited potent anticancer activity by activating ER stress in human NCI-H460 and A549 cells as well as in an in vivo models [ 42 ]. Hesperetin suppressed inflammatory responses in LPS-induced RAW 264.7 cells via the inhibition of NF-κB and the activation of the Nrf2/HO-1 pathways [ 43 ].…”

Xuefu Zhuyu decoction improves asthma‐induced asthenozoospermia based on network pharmacology and in vivo experiment

“…At the same time, different concentrations of Chrysin (25, 50 and 100 mg/kg BW) can increase serum albumin levels in rats and reduce liver and kidney toxicity markers (Pushpavalli et al., 2010). In addition, compounds such as Hispidulin also have certain biological activities such as anti‐oxidation and inhibition of cell apoptosis (Lv et al., 2020). In short, these compounds, or reduce inflammation, or increase ALB, or reduce asthma symptoms, or protect spermatozoa, prove that the various active ingredients in XFZYD have a certain therapeutic effect on asthenozoospermia caused by asthma.…”

Hispidulin modulates epithelial‑mesenchymal transition in breast cancer cells

“…Recent studies have shown that bioactive compounds in natural products have anticancer activities, and these substances can be effective in preventing and treating cancer (28). The natural compound hispidulin is a phenolic flavonoid found in Lamiaceae plants and has shown various effects against cancers (29)(30)(31)(32)(33). However, studies on the effect of hispidulin on EMT in breast cancer are limited.…”