Isorhamnetin Suppresses Human Gastric Cancer Cell Proliferation through Mitochondria-Dependent Apoptosis

Abstract

Derivates of natural products have been wildly utilized in the treatment of malignant tumors. Isorhamnetin (ISO), a most important active ingredient derived from flavonoids, shows great potential in tumor therapy. However, the therapeutic effects of ISO on gastric cancer (GC) remain unclear. Here, we demonstrate that ISO treatment dramatically inhibited the proliferation of two types of GC cells (AGS-1 and HGC-27) both in vitro and in vivo in time- and dose-dependent manners. These results are consistent with the transcriptomic analysis of ISO-treated GC cells, which yielded hundreds of differentially expressed genes that were enriched with cell growth and apoptosis. Mechanically, ISO treatment initiated the activation of caspase-3 cascade and elevated the expression of mitochondria-associated Bax/Bcl-2, cytosolic cytochrome c, followed by the activation of the cleavage of caspase-3 as well as poly ADP-ribose polymerase (PARP), resulting in the severe reduction of the mitochondrial potential and the accumulation of reactive oxygen species (ROS), while pre-treatment of the caspase-3 inhibitor could block the anti-tumor effect. Therefore, these results indicate that ISO treatment induces the apoptosis of GC cells through the mitochondria-dependent apoptotic pathway, providing a potential strategy for clinical GC therapy.

Nortriptyline hydrochloride, a potential candidate for drug repurposing, inhibits gastric cancer by inducing oxidative stress by triggering the Keap1-Nrf2 pathway

“…Initially, we investigated whether NTP has an inhibitory effect on GC cells by evaluating its cytotoxicity in AGS, SGC7901, MKN7, HGC27, and NCI-N87 cells. Based on the pre-experimental results of MTT and relevant reference literature 20 , we selected two commonly used GC cell lines with different degrees of differentiation for parallel validation experiments based on the effectiveness of NTP in different cell lines. One type of cell is undifferentiated HGC27 cells, and the other type is adenocarcinoma AGS cells.…”

A Comprehensive Study to Investigate the Tumor-Suppressive Role of Radix Bupleuri on Gastric Cancer with Network Pharmacology and Molecular Docking

“… 26 Isorhamnetin inhibits proliferation of human GC cells through mitochondria-dependent apoptosis. 27 Overall, the anticancer properties of these components may provide an important theoretical basis for the treatment of GC using Radix Bupleuri .…”

Selected Flavonols Targeting Cell Death Pathways in Cancer Therapy: The Latest Achievements in Research on Apoptosis, Autophagy, Necroptosis, Pyroptosis, Ferroptosis, and Cuproptosis

“…Studies conducted on many types of cancer prove the role of ISO in the regulatory processes of apoptosis. The basic parameters that change after the use of ISO are elevated expression of Bax and caspase-3, along with reduced expression of Bcl-2 [ 49 , 50 , 53 ].There is also an increase in the activity of caspase-8 and -9, as well as an increase in the release of cytochrome c from the mitochondrion to the cytosol [ 51 , 52 , 53 , 86 ]. Similarly to the previous flavonols, ISO can also regulate apoptosis through the PI3K/Akt pathway.…”