Chelerythrine suppresses proliferation and metastasis of human prostate cancer cells via modulating MMP/TIMP/NF-κB system

Yang, Baofeng; Zhang, Dongxu; Qian, Jiao; Cheng, Yufeng

doi:10.1007/s11010-020-03845-0

Cited by 21 publications

(18 citation statements)

References 34 publications

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“…As of now, the exact pathogenesis behind prostate cancer is still an urgent concern and determining the molecular mechanism is crucial for facilitating early clinical diagnosis and therapy. At present, chemotherapy, androgen ablation therapy, radiotherapy and radical prostatectomy are most commonly employed to manage localized disease of some patients with androgen-dependent prostate cancer at an early stage [ 5 ]. However, these therapy approaches are unsatisfactory for patients with advanced and aggressive prostate cancer, especially when this disease eventually progress into incurable hormone‑resistant subtype [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Puerarin induces apoptosis in prostate cancer cells via inactivation of the Keap1/Nrf2/ARE signaling pathway

Luo

et al. 2021

Bioengineered

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In this study, we examined the antitumor effects of Puerarin (PEU) on androgen-independent (DU145 and PC-3) and androgen-dependent (LNCaP) prostate cancer cells, and explored its potential mechanisms. Supplement with PEU (2.5 μM, 5 μM, and 10 μM) exhibited a marked inhibitory effect against the growth of DU145 and PC-3 cells, especially beyond 24 h, whereas there is only slight growth inhibitory effect on LNCaP cells at the high concentration of 10 μM at 72 h. This loss of cell viability in DU145 and PC-3 cells by PEU was mediated by the induction of apoptosis via up-regulation of Bax and cleaved-caspase-3, but downregulation of Bcl-2. Moreover, more intracellular ROS and LDH production were observed in DU145 and PC-3 cells upon PEU treatment. Meanwhile, the amount of pro-inflammatory cytokines (IL-1β and IL-6) was increased, but the content of anti-inflammatory cytokines IL-10 was attenuated. Additionally, PEU pretreatment resulted in an increase of Keap1 protein expression, and a decline of Nrf2, HO-1 and NQO1 protein expression in DU145 and PC3 cells. The present findings indicated that PEU exerted its antitumor activities toward androgen-independent prostate cancer cells via inactivation of Keap1/ NrF2/ARE signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Puerarin induces apoptosis in prostate cancer cells via inactivation of the Keap1/Nrf2/ARE signaling pathway

Luo

et al. 2021

Bioengineered

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“…Chelerythrine in vitro inhibited the proliferation of androgen-independent prostate cancer DU145 and PC-3 cell lines [20]. The obtained results indicated significant inhibition by chelerythrine in vitro invasion and metastasis of androgen-independent prostate cancer cells, at least in part, through the regulation of the protein expression of MMP/TIMP and disturbance of NF-κB activation.…”

Section: Introductionmentioning

confidence: 77%

Determination of Cytotoxic Activity of Sanguinaria canadensis Extracts against Human Melanoma Cells and Comparison of Their Cytotoxicity with Cytotoxicity of Some Anticancer Drugs

et al. 2021

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Melanoma is an enormous global health burden, and should be effectively addressed with better therapeutic strategies. Therefore, new therapeutic agents are needed for the management of this disease. The aim of this study was the investigation of cytotoxic activity of some isoquinoline alkaloid standards and extracts obtained from Sanguinaria canadensis—collected before, during, and after flowering—against three different human melanoma cells (A375, G361, SK-MEL-3). The cytotoxicity of these extracts was not previously tested on these melanoma cell lines. Determination of alkaloid contents was performed by HPLC-DAD using Polar RP column and mobile phase containing acetonitrile, water, and 1-butyl-3-methylimidazolium tetrafluoroborate. The cytotoxicity of alkaloid standards was investigated by determination of cell viability and calculation of IC50 values. Significant differences were observed in the alkaloids content and cytotoxic activity of the extracts, depending on the season of collection of the plant material. In the Sanguinaria canadensis extracts high contents of sanguinarine (from 4.8543 to 9.5899 mg/g of dry plant material) and chelerythrine (from 42.7224 to 6.8722 mg/g of dry plant material) were found. For both of these alkaloids, very high cytotoxic activity against the tested cell lines were observed. The IC50 values were in the range of 0.11–0.54 µg/mL for sanguinarine and 0.14 to 0.46 µg/mL for chelerythrine. IC50 values obtained for Sanguinaria canadensis extracts against all tested cell lines were also very low (from 0.88 to 10.96 µg/mL). Cytotoxic activity of alkaloid standards and Sanguinaria canadensis extracts were compared with the cytotoxicity of anticancer drugs—etoposide, cisplatin, and hydroxyurea. In all cases except the one obtained for cisplatin against A375, which was similar to that obtained for Sanguinaria canadensis after flowering against the same cell line, IC50 values obtained for anticancer drugs were higher than the IC50 values obtained for sanguinarine, chelerythrine, and Sanguinaria canadensis extracts. Our results showed that Sanguinaria canadensis extracts and isoquinoline alkaloids, especially sanguinarine and chelerythrine, could be recommended for further in vivo experiments in order to confirm the possibility of their application in the treatment of human melanomas.

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“…Another alkaloid structure, piperlongumine (Figure 6), appears to have anticancer properties via downregulating c-Met expression and NF-kB activity in renal, colon, lung, and prostate carcinoma cells (264)(265)(266)(267)(268). Harmine (269), fangchinoline (270), sinapine (271), gramine (272), cepharanthine (273), piperine (274,275), lamellarin D (276), ipobscurine (277), chelerythrine (278), dihydrochelerythrine (279), tryptanthrin (280), and neferine (Figure 6) (281) are some of the other alkaloid agents that exert significant anticancer activity through modulation of VEGF, AP-1, fibroblast growth factor receptor 4 (FGFR4)/ fibroblast growth factor receptor substrate 2a (FRS2a)-ERK1/ 2, NF-kB, Nrf-2/Kelch-like ECH-associated protein 1 (Keap-1), MMP-2, MMP-9, and STAT3.…”

Section: Alkaloidsmentioning

confidence: 99%

Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy

et al. 2022

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BackgroundTumors often progress to a more aggressive phenotype to resist drugs. Multiple dysregulated pathways are behind this tumor behavior which is known as cancer chemoresistance. Thus, there is an emerging need to discover pivotal signaling pathways involved in the resistance to chemotherapeutic agents and cancer immunotherapy. Reports indicate the critical role of the toll-like receptor (TLR)/nuclear factor-κB (NF-κB)/Nod-like receptor pyrin domain-containing (NLRP) pathway in cancer initiation, progression, and development. Therefore, targeting TLR/NF-κB/NLRP signaling is a promising strategy to augment cancer chemotherapy and immunotherapy and to combat chemoresistance. Considering the potential of phytochemicals in the regulation of multiple dysregulated pathways during cancer initiation, promotion, and progression, such compounds could be suitable candidates against cancer chemoresistance.ObjectivesThis is the first comprehensive and systematic review regarding the role of phytochemicals in the mitigation of chemoresistance by regulating the TLR/NF-κB/NLRP signaling pathway in chemotherapy and immunotherapy.MethodsA comprehensive and systematic review was designed based on Web of Science, PubMed, Scopus, and Cochrane electronic databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to include papers on TLR/NF-κB/NLRP and chemotherapy/immunotherapy/chemoresistance by phytochemicals.ResultsPhytochemicals are promising multi-targeting candidates against the TLR/NF-κB/NLRP signaling pathway and interconnected mediators. Employing phenolic compounds, alkaloids, terpenoids, and sulfur compounds could be a promising strategy for managing cancer chemoresistance through the modulation of the TLR/NF-κB/NLRP signaling pathway. Novel delivery systems of phytochemicals in cancer chemotherapy/immunotherapy are also highlighted.ConclusionTargeting TLR/NF-κB/NLRP signaling with bioactive phytocompounds reverses chemoresistance and improves the outcome for chemotherapy and immunotherapy in both preclinical and clinical stages.

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Chelerythrine suppresses proliferation and metastasis of human prostate cancer cells via modulating MMP/TIMP/NF-κB system

Cited by 21 publications

References 34 publications

Puerarin induces apoptosis in prostate cancer cells via inactivation of the Keap1/Nrf2/ARE signaling pathway

Puerarin induces apoptosis in prostate cancer cells via inactivation of the Keap1/Nrf2/ARE signaling pathway

Determination of Cytotoxic Activity of Sanguinaria canadensis Extracts against Human Melanoma Cells and Comparison of Their Cytotoxicity with Cytotoxicity of Some Anticancer Drugs

Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy

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