Paeonol‑mediated apoptosis of hepatocellular carcinoma cells by NF‑κB pathway

Abstract

The aim of the study was to investigate the effect of paeonol on the apoptosis of hepatocellular carcinoma cells and to explore the possible mechanism of its effect. During the experiment, the human hepatoma (Huh7) cell line was cultured and treated with different concentrations of paeonol. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the effects of paeonol at different concentrations on the proliferation of Huh7 cells after 24 h, and the optimal concentration of paeonol was selected for follow-up experiments. Huh7 cells were divided into the blank control group (C group), parthenolide [(an inhibitor of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB)] group (CE group), paeonol group (PO group), and paeonol + tumor necrosis factor-α (TNF-α) (an activator of NF-κB) group (PN group). The effect of paeonol on the apoptosis of Huh7 cells was detected via flow cytometry and Hoechst staining, respectively. The expression levels of NF-κB and protein apoptosis inhibitor-5 (p-API-5) were detected by semi-quantitative polymerase chain reaction (PCR) and western blot analysis, respectively, and the activity of NF-κB in cells was measured by NF-κB p65/50. After determination of the effects of paeonol at different concentrations on Huh7 cells by MTT assay, it was found that paeonol at the concentration of 200–800 µM could inhibit the proliferation of Huh7 cells (P<0.01), with 500 µM phenol being selected as the treatment concentration for follow-up experiments. Results of flow cytometry and Hoechst staining showed that the apoptotic levels of Huh7 cells in the PO and CE groups were significantly increased compared with that in the C group, and that in the PO group was higher than that in the PN group. The differences were statistically significant (P<0.01). Results of semi-quantitative PCR and western blot analysis revealed that the expression levels of NF-κB and p-API-5 in the PO and CE groups were significantly lower than those in the C group, and those in the PO group were lower than those in the PN group. The differences were statistically significant (P<0.01). The expression level of NF-κB p65/50 in the PO group was significantly lower than that in the C group (P<0.01). The results suggest that paeonol can significantly increase the apoptosis rate of Huh7 cells, and the possible mechanism of inducing apoptosis is related to the downregulation of NF-κB and p-API-5 and inhibition of the NF-κB signaling pathway.

Paeonol exerts anti‑tumor activity against colorectal cancer cells by inducing G0/G1 phase arrest and cell apoptosis via inhibiting the Wnt/β‑catenin signaling pathway

“…Induction of apoptosis is one of the most important and direct pathways that controls and eliminates cancer proliferation (11,34). The FcM results of the present study demonstrated that paeonol dose-and time-dependently induced cell apoptosis, which was in line with previous studies of cRc cells (29) and other cancer cells (11,31).…”

Paeonol induces antitumor effects in hepatocellular carcinoma cells through survivin via the cyclooxygenase-2/prostaglandin E2 signaling pathway

“…The results of the present study showed that paeonol significantly enhanced apoptosis and increased the sub-G1 fraction of HCC cells, a finding consistent with that of previous studies ( 11 , 26 ). The proliferation of HCC cells was also suppressed by paeonol, which confirmed a previous report that paeonol might induce HCC cell apoptosis via the NF-κB pathway ( 11 ). However, the effect of paeonol on survivin in HCC has not been previously examined.…”

“…Moreover, paeonol has been reported to exert antitumor activities in ovarian cancer cells ( 7 ), prostate cancer cells ( 8 ), breast cancer cells ( 9 ), and gastric cancer cells ( 10 ). Previous studies have shown that paeonol induces apoptosis of hepatoma cells via the nuclear factor kappa-B (NF-κB) pathway ( 11 ). Paeonol has also been shown to decrease oxidative injury and improve immunity in rats with HCC ( 12 ).…”

Paeonol Attenuates Methotrexate-Induced Cardiac Toxicity in Rats by Inhibiting Oxidative Stress and Suppressing TLR4-Induced NF-κB Inflammatory Pathway

“…Paeonol, a phenolic compound isolated from Paeonia suffruticosa, has been shown to have a wide range of pharmacological activities including antioxidant and anti-inflammatory properties [9] that may be beneficial in various diseases such as diabetes [10], cancer [11], gastric ulcer [12], liver fibrosis [13], and myocardial infarction [14]. Paeonol has been proven to have a protection against antineoplastic-induced toxicities such as cisplatin-induced nephrotoxicity [15] and epirubicininduced cardiac toxicity [16]; however, to date, this role has not been investigated in MTX-induced cardiac toxicity.…”