Polyphenols in Ilex latifolia Thunb. inhibit human lung cancer cell line A549 by regulation of the PI3K-Akt signaling pathway

Abstract

Background The leaves of the plant Ilex latifolia Thunb. can be made into Kuding tea, which is a drink rich in polyphenols. This study aimed to observe the effect of Ilex latifolia Thunb. polyphenols (ILTPs) on human lung cancer cell line A549 (A549 cells) by regulating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Methods In vitro cultured cells were treated with ILTPs; the proliferation of A549 cells and BEAS-2B human normal lung epithelial cells (Beas-2B cells) was observed using the 3-(4,5-dimethylazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the survival status of A549 cells was observed by fluorescence staining. The expression of A549 cells was observed by quantitative polymerase chain reaction (qPCR) assay and Western blot analysis, while the compound composition of ILTPs was detected using high-performance liquid chromatography (HPLC). Results The experimental results showed that the proliferation of Beas-2B cells was unaffected by treatment with 0–500 μg/mL of ILTPs, whereas the decreased proliferation of A549 cells was observed with the increasing concentrations of ILTPs. Additionally, ILTPs elevated the levels of lactate dehydrogenase (LDH) and reactive oxygen species (ROS) and promoted apoptosis in A549 cells. The results of qPCR experiments showed that ILTPs upregulated caspase-9 mRNA expression and downregulated phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), B-cell lymphoma-2 (Bcl-2), nuclear factor-κB (NF-κB), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 alpha (HIF-1α), and cyclooxygenase-2 (COX-2) expression in A549 cells. The Western blot analysis results also showed that ILTPs could reduce the protein expression of PI3K and Akt. The HPLC results showed that the main compounds present in the ILTPs were rutin, kaempferol, isochlorogenic acid A, isochlorogenic acid B, and isochlorogenic acid C. Conclusions Thus, this study indicated that the polyphenols of I. latifolia act as a class of natural functional food materials that potently suppress cancer by exerting their inhibitory effects on A549 cell proliferation through five key polyphenolic compounds.

Effect of ferulic acid and p‐coumaric acid on lowering uric acid through network pharmacology and in vitro studies

“…The results of enrichment analysis showed that the pathways associated with UA lowering were the PI3K/Akt, estrogen, NF‐κB, HIF‐1, prolactin, and adipocytokine signaling pathways; the most significant pathway was the PI3K/Akt signaling pathway. The PI3K/Akt signaling pathway is involved in cell proliferation, cell differentiation, apoptosis, and migration processes in various tissues of the body and plays an important role in hyperuricemia inflammatory diseases and tumor diseases, making them hot research topics in recent years (Chen et al., 2022). It has been shown that UA can activate the PI3K/Akt pathway, thus causing inflammatory damage to cells (Xin et al., 2018).…”

“…Hyperuricemia often parallels metabolic syndrome, which in turn has insulin resistance as the pathological basis, with clinical manifestations including metabolic disorders of blood glucose, blood pressure, blood lipids, and cardiovascular diseases(Gabriela et al, 2018) explaining the biological processes involved in the target.The results of enrichment analysis showed that the pathways associated with UA lowering were the PI3K/Akt, estrogen, NF-κB, HIF-1, prolactin, and adipocytokine signaling pathways; the most significant pathway was the PI3K/Akt signaling pathway. The PI3K/Akt signaling pathway is involved in cell proliferation, cell differentiation, apoptosis, and migration processes in various tissues of the body and plays an important role in hyperuricemia inflammatory diseases and tumor diseases, making them hot research topics in recent years(Chen et al, 2022). It has been shown that UA can activate the PI3K/Akt pathway, thus causing inflammatory damage to cells(Xin et al, 2018).Compounds could alleviate hyperuricemia by regulating pathway protein levels.…”

Association between tea consumption and quality of life in men with esophageal squamous carcinoma based on TTD model

“…Tea is high in avonoids, alkaloids, phenols, theanine, and other compounds, particularly tea polyphenols, which have antioxidant, anticancer, anti-in ammatory, antibacterial, anti-angiogenic, and apoptotic properties (Chen et al 2021). Tea polyphenols can play an anti-cancer role by scavenging free radicals, blocking lipid peroxidation, and increasing the activity of enzymes in the body (Chen et al 2022b). Tea leaf extracts, such as epigallocatechin and theanine, have been shown to inhibit the development and progression of gastrointestinal tumors such as colorectal cancer (Ma et al 2022), esophageal cancer (Nechuta et al 2012), and gastric cancer (Yuan et al 2020) by regulating various signaling pathways (Alam et al 2022), initiating apoptosis, inhibiting in ammatory pathways, and suppressing oxidative stress, among other mechanisms.…”

Improvement of postoperative quality of life in patients with esophageal squamous cell carcinoma: does tea consumption have a role?

“…Tea is high in flavonoids, alkaloids, phenols, theanine, and other compounds, particularly tea polyphenols, which have antioxidant, anticancer, anti-inflammatory, antibacterial, anti-angiogenic, and apoptotic properties [7]. Tea polyphenols can play an anti-cancer role by scavenging free radicals, blocking lipid peroxidation, and increasing the activity of enzymes in the body [8]. Tea leaf extracts, such as epigallocatechin and theanine, have been shown to inhibit the development and progression of gastrointestinal tumors such as colorectal cancer [9], esophageal cancer [10], and gastric cancer [11] by regulating various signaling pathways [12], initiating apoptosis, inhibiting inflammatory pathways, and suppressing oxidative stress, among other mechanisms.…”