Hyperoside Induces Breast Cancer Cells Apoptosis via ROS-Mediated NF-κB Signaling Pathway

Abstract

Hyperoside (quercetin 3-o-β-d-galactopyranoside) is one of the flavonoid glycosides with anti-inflammatory, antidepressant, and anti-cancer effects. But it remains unknown whether it had effects on breast cancer. Here, different concentrations of hyperoside were used to explore its therapeutic potential in both breast cancer cells and subcutaneous homotransplant mouse model. CCK-8 and wound healing assays showed that the viability and migration capability of Michigan Cancer Foundation-7 (MCF-7) and 4T1 cells were inhibited by hyperoside, while the apoptosis of cells were increased. Real-time quantitative PCR (qRT-PCR) and western blot analysis were used to detect mRNA and the protein level, respectively, which showed decreased levels of B cell lymphoma-2 (Bcl-2) and X-linked inhibitor of apoptosis (XIAP), and increased levels of Bax and cleaved caspase-3. After exploration of the potential mechanism, we found that reactive oxygen species (ROS) production was reduced by the administration of hyperoside, which subsequently inhibited the activation of NF-κB signaling pathway. Tumor volume was significantly decreased in subcutaneous homotransplant mouse model in hyperoside-treated group, which was consistent with our study in vitro. These results indicated that hyperoside acted as an anticancer drug through ROS-related apoptosis and its mechanism included activation of the Bax–caspase-3 axis and the inhibition of the NF-κB signaling pathway.

10-HDA Induces ROS-Mediated Apoptosis in A549 Human Lung Cancer Cells by Regulating the MAPK, STAT3, NF-κB, and TGF-β1 Signaling Pathways

“…ROS, as a natural by-product of aerobic respiration, is closely related to cell apoptosis, cell cycle, signal transduction cascade, protein phosphorylation, and cytoskeleton formation [ 31 , 32 ]. Increased ROS stimulates the cancer-related signal transduction pathway and enhances the survival and proliferation of cancer cells [ 33 ]. ROS can also be used as a signaling molecule to transduce extracellular stimulus signals, directly inducing apoptosis or indirectly participating in intracellular signal transduction [ 34 ].…”

Targeting ferroptosis in breast cancer

“…Lipid peroxidation is the main killer in the process of ferroptosis, which could derive from lipids by being "attacked" by intracellular ROS [18]. ROS is also a potent driver of apoptosis in breast cancer [116], and multiple drugs induce apoptosis via ROSmediated pathways [117][118][119][120][121][122]. Cystine starvation has been shown to induce ferroptosis in breast cancer cells as described above [79].…”

<p>Hyperin Controls the Development and Therapy of Gastric Cancer via Regulating Wnt/β-Catenin Signaling</p>

“…Qiu et al found that hyperoside acted as an anticancer drug through ROS-related apoptosis and its mechanism included activation of the Baxcaspase-3 axis and the inhibition of the NF-κB signaling pathway. 23 Li et al showed that hyperoside and microRNA-let7a-5p might provide a synergistic effect on anti-cancer, which may provide a new idea for lung cancer treatment. 10 Liu et al indicated that hyperoside completely impeded tumor growth through angiogenesis inhibition.…”