Therapeutic Potential of Berberine in the Treatment of Glioma: Insights into Its Regulatory Mechanisms

Asemi, Zatollah; Behnam, Mohammad; Pourattar, Mohammad Ali; Mirzaei, Hamed; Razavi, Zahra; Tamtaji, Omid Reza

doi:10.1007/s10571-020-00903-5

Cited by 11 publications

(8 citation statements)

References 80 publications

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“…Berberine has anti-inflammatory, blood-sugar-lowering, anti-microbial, and anti-tumor effects. 19 , 21 Berberine has been used for many years as a non-prescription drug for the treatment of bacterial diarrhea in China 36 . Berberine is also considered a potential drug for the treatment of hyperlipidemia and diabetes, which has been proved in many clinical trials.…”

Section: Discussionmentioning

confidence: 99%

“… 20 In addition, berberine has been proved to regulate autophagy, apoptosis, invasion and chemotherapy sensitization of glioma cells in various ways. 21 In this study, we tested the inhibitory effects of berberine on U87 and U251 cells. Our results indicated that berberine inhibited the proliferation of glioma cells, and this inhibitory ability presented the concentration dependence and time dependence.…”

Section: Discussionmentioning

confidence: 99%

“…17,18 In addition, berberine has been shown to have anti-cancer properties and can suppress the growth of cancer cells in gastric, bladder, colon, glioma, breast, melanoma, pancreatic, endometrial, and lung cancers. [19][20][21] Studies have demonstrated that berberine exerts anti-cancer effects by regulating MAPK, Erk1/2, JNK, AKT, and Wnt/β-catenin signaling pathways. 20,22 However, the role of berberine in signaling pathways downstream of wtp53 and mutp53 is unclear.…”

Section: Introductionmentioning

confidence: 99%

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<p>Berberine Inhibits Cell Proliferation by Interfering with Wild-Type and Mutant P53 in Human Glioma Cells</p>

Liu¹,

Chen²,

Gao³

et al. 2020

OTT

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Introduction: Glioma is the most common malignant brain tumor. TP53 is the most common mutant gene in human cancer. Wild-type p53 (wtp53) is a tumor suppressor protein whereas mutant p53 (mutp53) is an oncoprotein that promotes tumor cell proliferation. Our aim was to examine the inhibitory effects of berberine on the proliferation of human glioma cells via regulation of wtp53, mutp53, and their downstream molecules. Methods: We selected wtp53 cells (U87 cells) and mutp53 cells (U251 cells termed p53 R273H) to examine the inhibitory effects of berberine on human glioma cells. We used the CCK-8 kit to detect the toxic effect of berberine. Flow cytometry was used to detect the effect of berberine. Clone formation test was used to test the inhibitory effect of berberine on the proliferation of glioma cells. Western blot was used to detect the changes of related proteins such as p53, p-p53, p21 and cyclin D1. Lentivirus transduction was used to transduce wild-type p53 into U251 cells to further examine the effect of berberine. The nude mouse subcutaneous tumor model was used to detect the effect of berberine on inhibiting the proliferation of glioma cells in vivo. Results: Berberine promoted the phosphorylation of wtp53, increased the expression of p21 protein, reduced cyclin D1 content, and caused G1 phase arrest in U87 cells. Berberine also reduced mutp53 content and caused G2 phase arrest in U251 cells with a concurrent decrease in p21, cyclin D1, and cyclin B1 content. Transduction with wtp53 enhanced the effects on cell cycle arrest. Further, berberine significantly inhibited glioma growth in vivo mouse tumor model. Discussion: Glioma is a group of heterogeneous brain tumors with unique biological and clinical characteristics. Berberine can inhibit glioma cells through a variety of ways. Our research indicated that berberine inhibited the proliferation of glioma cells by interfering with wtp53 and mutp53. This indicates that berberine could be used as a potential drug to treat wild-type and mutant p53 glioma.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

<p>Berberine Inhibits Cell Proliferation by Interfering with Wild-Type and Mutant P53 in Human Glioma Cells</p>

Liu¹,

Chen²,

Gao³

et al. 2020

OTT

View full text Add to dashboard Cite

show abstract

“…These plants have been used for thousands of years ( Wang et al, 2019a ; Fan et al, 2019 ). Studies have shown that berberine has a variety of pharmacological activities, including anti-microbial, anti-tumor, lowering glucose, lowering cholesterol, anti-inflammatory, antioxidant, immunomodulatory and neuroprotective effects ( Asemi et al, 2020 ; Song et al, 2020 ). So far, the neuroprotective effect of berberine has been involved ( Lin and Zhang 2018 ).…”

Section: Methodsmentioning

confidence: 99%

Neuroprotective Effect for Cerebral Ischemia by Natural Products: A Review

Xie

et al. 2021

Front. Pharmacol.

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Natural products have a significant role in the prevention of disease and boosting of health in humans and animals. Stroke is a disease with high prevalence and incidence, the pathogenesis is a complex cascade reaction. In recent years, it’s reported that a vast number of natural products have demonstrated beneficial effects on stroke worldwide. Natural products have been discovered to modulate activities with multiple targets and signaling pathways to exert neuroprotection via direct or indirect effects on enzymes, such as kinases, regulatory receptors, and proteins. This review provides a comprehensive summary of the established pharmacological effects and multiple target mechanisms of natural products for cerebral ischemic injury in vitro and in vivo preclinical models, and their potential neuro-therapeutic applications. In addition, the biological activity of natural products is closely related to their structure, and the structure-activity relationship of most natural products in neuroprotection is lacking, which should be further explored in future. Overall, we stress on natural products for their role in neuroprotection, and this wide band of pharmacological or biological activities has made them suitable candidates for the treatment of stroke.

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“…Liver cancer is the fourth leading cause of cancer-related deaths and sixth most common cancer in the world, with high prevalence in East Asia, South-Eastern Asia, and Northern and Western Africa 1 , 2 . The most common histological types of primary liver cancer are hepatocellular carcinoma (HCC) (80%) and intrahepatic cholangiocarcinoma (iCCA) (10–15%) 3 .…”

Section: Introductionmentioning

confidence: 99%

The short-term safety and efficacy of TANDEM microspheres of various sizes and doxorubicin loading concentrations for hepatocellular carcinoma treatment

Lin

Liu

Pan

et al. 2021

Sci Rep

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Drug-eluting bead transarterial chemoembolization (DEB-TACE) is the most common treatment for unresectable hepatocellular carcinoma (HCC). However, the effect of drug loading concentration and microsphere size on treatment outcomes remains unclear. This retrospective study compares the outcomes of 87 HCC patients who underwent DEB-TACE with half-loaded or full-loaded doxorubicin (maximum capacity 50 mg/mL) in 75-µm or 100-µm microspheres. Treatment with 100-μm microspheres resulted in significantly lower rates of procedure-related complications (6.6% vs. 26.9%; P < 0.05), post-embolization syndrome (32.8% vs. 61.5%, P < 0.05), SIR complications (32.8% vs. 61.5%; P < 0.01) and adverse events involving abdominal pain (19.7% vs. 42.3%; P < 0.05). Half-load doxorubicin microspheres resulted in greater treatment response (OR, 4.00; 95% CI 1.06–15.13; P, 0.041) and shorter hospital stays (OR, − 1.72; 95% CI − 2.77–0.68; P, 0.001) than did microspheres loaded to full capacity. Stratified analysis further showed that patients treated with 100-μm half-load doxorubicin microspheres had a higher CR (63.6% vs 18.0%) and ORR (90.9 vs 54.0%) and a shorter hospital stay (1.6 ± 1.3 vs 4.2 ± 2.3 days) than did those treated with full-load microspheres (P < 0.05). Thus, the drug-loading concentration of microspheres in DEB-TACE should be carefully considered.

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Therapeutic Potential of Berberine in the Treatment of Glioma: Insights into Its Regulatory Mechanisms

Cited by 11 publications

References 80 publications

<p>Berberine Inhibits Cell Proliferation by Interfering with Wild-Type and Mutant P53 in Human Glioma Cells</p>

<p>Berberine Inhibits Cell Proliferation by Interfering with Wild-Type and Mutant P53 in Human Glioma Cells</p>

Neuroprotective Effect for Cerebral Ischemia by Natural Products: A Review

The short-term safety and efficacy of TANDEM microspheres of various sizes and doxorubicin loading concentrations for hepatocellular carcinoma treatment

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