Berberine Targets AP-2/hTERT, NF-κB/COX-2, HIF-1α/VEGF and Cytochrome-c/Caspase Signaling to Suppress Human Cancer Cell Growth

Fu, Lingyi; Chen, Wangbing; Guo, Wei; Wang, Jingshu; Tian, Yun; Shi, Dingbo; Zhang, Xiaohong; Qiu, Huijuan; Xiao, Xia; Kang, Tiebang; Huang, Wenlin; Wang, Shusen; Deng, Wuguo

doi:10.1371/journal.pone.0069240

Cited by 99 publications

(74 citation statements)

References 45 publications

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“…Berberine has been reported to inhibit topoisomerase II enzyme in vitro [54]. The other possibility of berberine-induced cell killing seems to be due to the trans activation of nuclear factor-κB (NF-κB), and cyclo-oxygenase II, and suppression of activator protein 1, cyclins, Akt, p53 and PARP and induction apoptosis [37,40,[55][56][57][58].…”

Section: Discussionmentioning

confidence: 99%

Isoquinoline Alkaloid Berberine Exerts its Antineoplastic Activity by Inducing Molecular DNA Damage in HeLa Cells: A Comet Assay Study

Ch¹,

Jagetia²,

Rao³

2014

Biol Med (Aligarh)

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Molecular damage of DNA plays an important role in the cell killing and several anti-neoplastic agents exert their cytotoxic effects by inducing DNA damage in the cancer cells. DNA damaging effect of various concentrations of berberine chloride (BCL), an isoquinoline alkaloid was studied in HeLa cells by alkaline comet assay. The DNA damage has been expressed as olive tail moment (OTM). Incubation of HeLa cells with BCL for 4 h showed greater amount of DNA damage (OTM) than 2 h treatment. BCL treatment caused a concentration dependent rise in the DNA damage in HeLa cells and exposure of HeLa cells with 1 µg/ml BCL caused a10 fold rise in baseline DNA damage, whereasa maximum rise in DNA damage was observed in HeLa cells exposed to 8 µg/ml BCL. The study of DNA repair kinetics at different BCL post-treatment times revealed a constant rise in the DNA damage in BCL treated cells up to 24 h except for 1 -4 µg/ml BCL, where the highest DNA damage was observed at 12 h post-BCL treatment. The clonogenic assay showed that BCL treatment resulted in a concentration dependent rise in its cell killing effect. The cell survival and molecular DNA damage in HeLa cells treated with BCL has an inverse correlation indicating that with increased DNA damage cell survival declined. Our study demonstrates that anti-neoplastic effect of BCL is mainly due to its ability to cause damage to the cellular genome.

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Section: Discussionmentioning

confidence: 99%

Isoquinoline Alkaloid Berberine Exerts its Antineoplastic Activity by Inducing Molecular DNA Damage in HeLa Cells: A Comet Assay Study

Ch¹,

Jagetia²,

Rao³

2014

Biol Med (Aligarh)

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“…The present study detected VEGF, PEDF, Cox-2, AKT, p-AKT, E-cadherin, RhoA and RhoC, which are associated with tumor apoptosis, growth, invasion and metastasis (18)(19)(20). The results revealed that the expression of all the above factors was increased or decreased when shET-1 and Endostar were present or absent.…”

Section: Discussionmentioning

confidence: 51%

Effects of silencing endothelin-1 on invasion and vascular formation in lung cancer

Zhang

Chen

et al. 2017

Oncology Letters

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Abstract. Endothelin-1 (ET-1), which exists not only in the vascular endothelium but is also widely present in various tissues and cells, is an important cardiovascular regulatory factor that serves an important role in maintaining the basal vascular tone and homeostasis in the cardiovascular system. In the present study, the ET-1 gene was silenced by RNA interference, and the effects on lung cancer cell proliferation and tumor cell invasion were then detected by Cell Counting kit-8 and Transwell assays. In addition, the expression of apoptosis, growth and invasion-associated proteins, including RhoA/C, vascular endothelial growth factor, pigment epithelium-derived factor, AKT, E-cadherin and cyclooxygenase-2 was evaluated by western blotting upon silencing ET-1. In the present study, Endostar, a recombinant human endostatin injectable drug, was also used, and it was assessed whether the sensitivity of tumor cells to this drug could be increased by silencing ET-1. Both in vivo and in vivo tests were carried out in the present study. The experimental data indicated that ET-1 silencing can inhibit tumor cell proliferation and invasion, particularly in the presence of Endostar.

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“…12B). Recently, Fu et al demonstrated that berberine inhibited human nonsmall cell lung cancer cell growth by simultaneously targeting NF-κB/COX-2, PI3K/Akt and caspase signalling pathways (58). Furthermore, others studies showed an antitumor effect of berberine via inhibition of NK-κB pathway and induction of apoptosis (59,60).…”

Section: Resultsmentioning

confidence: 99%

Berberis libanotica extract targets NF-κB/COX-2, PI3K/Akt and mitochondrial/caspase signalling to induce human erythroleukemia cell apoptosis

Diab

Fidanzi

Léger

et al. 2015

International Journal of Oncology

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Abstract. The aim of this study was to describe and understand the relationship between cyclooxygenase-2 (COX-2) expression and apoptosis rate in erythroleukemia cells after apoptosis induction by Berberis libanotica (Bl) extract. To achieve this goal we used erythroleukemia cell lines expressing COX-2 (HEL cell line) or not (K562 cell line). Moreover, we made use of COX-2 cDNA to overexpress COX-2 in K562 cells. In light of the reported chemopreventive and chemosensitive effects of natural products on various tumor cells and animal models, we postulated that our Bl extract may mediate their effects through apoptosis induction with suppression of cell survival pathways. Our study is the first report on the specific examination of intrinsic apoptosis and Akt/NF-κB/COX-2 pathways in human erythroleukemia cells upon Bl extract exposure. Even if Bl extract induced apoptosis of three human erythroleukemia cell lines, a dominant effect of Bl extract treatment on K562 cells was observed resulting in activation of the late markers of apoptosis with caspase-3 activation, PARP cleavage and DNA fragmentation. Whereas, we showed that Bl extract reduced significantly expression of COX-2 by a dose-dependent manner in HEL and K562 (COX-2 + ) cells. Furthermore, in regard to our results, it is clear that the simultaneous inhibition of Akt and NF-κB signalling can significantly contribute to the anticancer effects of Bl extract in human erythroleukemia cells. We observed that the Bl extract is clearly more active than the berberine alone on the induction of DNA fragmentation in human erythroleukemia cells.

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Berberine Targets AP-2/hTERT, NF-κB/COX-2, HIF-1α/VEGF and Cytochrome-c/Caspase Signaling to Suppress Human Cancer Cell Growth

Cited by 99 publications

References 45 publications

Isoquinoline Alkaloid Berberine Exerts its Antineoplastic Activity by Inducing Molecular DNA Damage in HeLa Cells: A Comet Assay Study

Isoquinoline Alkaloid Berberine Exerts its Antineoplastic Activity by Inducing Molecular DNA Damage in HeLa Cells: A Comet Assay Study

Effects of silencing endothelin-1 on invasion and vascular formation in lung cancer

Berberis libanotica extract targets NF-κB/COX-2, PI3K/Akt and mitochondrial/caspase signalling to induce human erythroleukemia cell apoptosis

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