Anticancer activity of bergenin against cervical cancer cells involves apoptosis, cell cycle arrest, inhibition of cell migration and the STAT3 signalling pathway

Shi, Xiaoshun; Xu, Manman; Luo, Kai; Huang, Weidong; Yu, Honggang; Zhou, Tongchong

doi:10.3892/etm.2019.7380

Cited by 18 publications

(17 citation statements)

References 10 publications

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“…The results indicated that bergenin may inhibit the EMT in bladder cancer. Previous studies indicated that Bergenin exerted anti‐cancer effects by inhibiting the viability, migration, and invasion and inducing cell cycle arrest and apoptosis in cervical cancer cells (Shi et al, 2019). The present study revealed that bergenin could act as a tumor suppressor in bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported to exhibit a diversity of pharmacological properties, including anti‐inflammatory, anti‐oxidation, anti‐diabetes, and neuroprotective effects (Barai et al, 2019; Kumar et al, 2012; Lopes de Oliveira et al, 2019; Qiao et al, 2019). Recent studies indicated that bergenin exhibited significant pharmacological activities such as anticancer (Shi et al, 2019). However, whether Bergenin affects the development of bladder cancer remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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Bergenin inhibits bladder cancer progression via activating the PPARγ/PTEN/Akt signal pathway

Liu

Zhang

et al. 2020

Drug Development Research

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Bladder cancer is one of the most common malignant tumors in the urinary system with high mortality and morbidity. Evidence revealed that bergenin could affect the development of cancer. Here, we aimed to investigate the effect of bergenin on bladder cancer progression and its mechanism. The effect of bergenin on cell function was first detected, followed by assessing the changes of the epithelial‐mesenchymal transition (EMT) in bergenin‐treated cells. The effect of bergenin on peroxisome proliferator‐activated receptor γ (PPARγ)/phosphatase and tensin homolog (PTEN)/Akt signal pathway was measured by Western blotting, followed by the rescue experiments. The results showed that bergenin treatment significantly decreased cell viability and increased G1 phase arrest, accompanied by reduced expression of Ki67, cycling D1, and cycling B1 in bladder cancer cells. Apoptosis was induced by bergenin in bladder cancer cells, as evidenced by increased Bax and cleaved caspase 3 protein levels and decreased Bcl‐2 level in bergenin‐treated cells. Meanwhile, the inhibition of the invasion, migration, and EMT was also observed in bergenin‐treated cells. Mechanism studies showed that bergenin treatment could activate PPARγ/PTEN/Akt signal pathway, as evidence by the increased nucleus PPARγ and phosphatase and tensin homolog (PTEN) expression and decreased Akt expression. Moreover, PPARγ inhibitor administration inverted the effects of bergenin on bladder cancer cell function, including the proliferation, apoptosis, invasion, and migration in bladder cancer cells. Our findings revealed that bergenin could inhibit bladder cancer progression via activating the PPARγ/PTEN/Akt signal pathway, indicating that bergenin may be a potential therapeutic medicine for bladder cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bergenin inhibits bladder cancer progression via activating the PPARγ/PTEN/Akt signal pathway

Liu

Zhang

et al. 2020

Drug Development Research

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“…Interestingly, the other phytochemicals tested in this study, i.e. arctigenin, bergenin and xanthohumol induced apoptosis in several cancer cells [26][27][28]. However, all these compounds, similarly as (+)-usnic acid, particularly at lower concentration (2 µM) reduced the level of Bax gene transcript but did not affect its protein in FaDu cells.…”

Section: B Cmentioning

confidence: 76%

(+)-Usnic acid modulates the Nrf2-ARE pathway in FaDu hypopharyngeal carcinoma cells

et al. 2021

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Naturally occurring phytochemicals of different origin and structure, arctigenin, bergenin, usnic acid and xanthohumol, were shown to affect Nrf2 pathway in the context of various diseases, but their effect on this pathway in cancer cells was not extensively investigated. This study aimed to evaluate the effect of these compounds on Nrf2 expression and activation in hypopharyngeal FaDu squamous cell carcinoma cells. FaDu cells were treated with 2 or 10 μM arctigenin, bergenin, (+)-usnic acid or xanthohumol for 24 h. While arctigenin, bergenin, and xanthohumol did not affect either Nrf2 expression or activation, (+)-usnic acid treatment increased its transcript level and increased the nuclear/cytosol Nrf2 protein ratio—the measure of Nrf2 pathway activation. Consequently, (+)-usnic acid enhanced the transcription and translation of Nrf2 target genes: NQO1, SOD, and to a lesser extent, GSTP. The treatment of FaDu cells with (+)-usnic acid decreased both GSK-3β transcript and protein level, indicating its possible involvement in Nrf2 activation. All the tested compounds decreased Bax mRNA but did not change the level of Bax protein. (+)-Usnic acid tended to increase the percentage of early apoptotic cells and LC3 protein, autophagy marker. Significant induction of p53 also was observed after treatment with (+)-usnic acid. In summary, the results of this study indicate that low concentrations of (+)-usnic acid activate Nrf2 transcription factor, most probably as a result of ROS accumulation, but do not lead to FaDu hypopharyngeal carcinoma cells death.

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“…Bergenin ( Figure 1 ) is a naturally occurring C-glucoside of 4-O-methylgallic acid found in many plant species. Several therapeutic applications of bergenin have been proposed in the literature, e.g., anti-ulcerative [ 10 ], hepatoprotective [ 11 , 12 ], anticancer [ 13 ], neuroprotective [ 14 , 15 ], antidiabetic [ 16 ], anti-inflammatory [ 17 , 18 , 19 , 20 , 21 , 22 ], antinociceptive [ 17 , 23 ], and antioxidant [ 12 , 16 , 24 , 25 , 26 , 27 ]. Considering that oxidative stress and neuroinflammation play key roles in the pathophysiology of DN [ 28 ], the above-mentioned properties of bergenin may contribute to the effective control of painful DN.…”

Section: Introductionmentioning

confidence: 99%

Bergenin Reduces Experimental Painful Diabetic Neuropathy by Restoring Redox and Immune Homeostasis in the Nervous System

Villarreal

Santos

Lauria

et al. 2020

IJMS

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Diabetic neuropathy is a frequent complication of diabetes. Symptoms include neuropathic pain and sensory alterations—no effective treatments are currently available. This work characterized the therapeutic effect of bergenin in a mouse (C57/BL6) model of streptozotocin-induced painful diabetic neuropathy. Nociceptive thresholds were assessed by the von Frey test. Cytokines, antioxidant genes, and oxidative stress markers were measured in nervous tissues by ELISA, RT-qPCR, and biochemical analyses. Single (3.125–25 mg/kg) or multiple (25 mg/kg; twice a day for 14 days) treatments with bergenin reduced the behavioral signs of diabetic neuropathy in mice. Bergenin reduced both nitric oxide (NO) production in vitro and malondialdehyde (MDA)/nitrite amounts in vivo. These antioxidant properties can be attributed to the modulation of gene expression by the downregulation of inducible nitric oxide synthase (iNOS) and upregulation of glutathione peroxidase and Nrf2 in the nervous system. Bergenin also modulated the pro- and anti-inflammatory cytokines production in neuropathic mice. The long-lasting antinociceptive effect induced by bergenin in neuropathic mice, was associated with a shift of the cytokine balance toward anti-inflammatory predominance and upregulation of antioxidant pathways, favoring the reestablishment of redox and immune homeostasis in the nervous system. These results point to the therapeutic potential of bergenin in the treatment of painful diabetic neuropathy.

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Anticancer activity of bergenin against cervical cancer cells involves apoptosis, cell cycle arrest, inhibition of cell migration and the STAT3 signalling pathway

Cited by 18 publications

References 10 publications

Bergenin inhibits bladder cancer progression via activating the PPARγ/PTEN/Akt signal pathway

Bergenin inhibits bladder cancer progression via activating the PPARγ/PTEN/Akt signal pathway

(+)-Usnic acid modulates the Nrf2-ARE pathway in FaDu hypopharyngeal carcinoma cells

Bergenin Reduces Experimental Painful Diabetic Neuropathy by Restoring Redox and Immune Homeostasis in the Nervous System

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