Chrysin Inhibits Tumor Promoter-Induced MMP-9 Expression by Blocking AP-1 via Suppression of ERK and JNK Pathways in Gastric Cancer Cells

Xia, Yong; Lian, Sen; Khoi, Pham Ngoc; Yoon, Hyun Joong; Joο, Young Eun; Chay, Kee-Oh; Kim, Kyung Keun; Jung, Young Do

doi:10.1371/journal.pone.0124007

Cited by 67 publications

(53 citation statements)

References 37 publications

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“…14,16,32 In the present study, chrysinNPs were observed to have anticancer effects in A549-derived tumor tissues. In fact, chrysin-NPs inhibited cell proliferation and induced apoptosis in tumor tissues ( Figure 6).…”

Section: Discussionmentioning

confidence: 49%

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Improved chemotherapeutic efficacy of injectable chrysin encapsulated by copolymer nanoparticles

Kim¹,

Lim

Shim³

et al. 2017

IJN

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Chrysin is a flavone that is found in several plants and in honeycomb and possesses various biological activities. However, its low solubility means it has poor bioavailability, which must be resolved to enable its pharmaceutical applications. In the present study, chrysin was incorporated into methoxy poly(ethylene glycol)-β-polycaprolactone nanoparticles (chrysin-NPs) using the oil-in-water technique in order to overcome problems associated with chrysin. The properties of chrysin-NPs were analyzed, and their anticancer effects were investigated in vitro and in vivo. Chrysin-NPs were 77 nm sized (as determined by dynamic laser light scattering) and showed a monodisperse distribution. The zeta potential of chrysin-NPs was −2.22 mV, and they were spherically shaped by cryo-transmission electron microscopy (cryo-TEM). The loading efficiency of chrysin-NPs was 46.96%. Chrysin-NPs retained the cytotoxicity of chrysin in A549 cells. The therapeutic efficacies of chrysin-NPs were compared with those of chrysin in an A549-derived xenograft mouse model. Chrysin-NPs were intravenously injected at a 10 times lower dosage than chrysin 3 times per week (q2d×3/week). However, free chrysin was orally administrated 5 times per week (q1d×5/week). Chrysin-NP-treated group showed significant tumor growth delay, which was similar to that of chrysin-treated group, despite the considerably lower total dosage. These results suggest that the injectable chrysin-NPs enhance therapeutic efficacy in vivo and offer a beneficial formulation for chemotherapy.

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Section: Discussionmentioning

confidence: 49%

“…Chrysin is a natural active component found in various herbs, mushroom, and propolis 2 and has anti-inflammatory, 3,4 antiaging, 5 antiviral, 6 antioxidant, [7][8][9] antidiabetes, 10 antiaromatase, 11,12 and anticancer [13][14][15][16] activities. Accordingly, it is widely held that chrysin has potential pharmaceutical applications.…”

Section: Introductionmentioning

confidence: 99%

Improved chemotherapeutic efficacy of injectable chrysin encapsulated by copolymer nanoparticles

Kim¹,

Lim

Shim³

et al. 2017

IJN

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show abstract

“…Generally, a crucial c-Jun and c-Fos binding site, AP-1 is located in the promoter region of inducible type of MMP genes. Blocking in the AP-1 binding activity prevents tumor promoter-induced MMP-9 transcription [45]. Besides, NF-κB and SP-1 transcription factors also play a co-activators role in the regulation of MMP-2 and MMP-9 [46, 47].…”

Section: Discussionmentioning

confidence: 99%

Nobiletin inhibits human osteosarcoma cells metastasis by blocking ERK and JNK-mediated MMPs expression

et al. 2016

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Nobiletin, a polymethoxyflavone, has a few pharmacological activities, including anti-inflammation and anti-cancer effects. However, its effect on human osteosarcoma progression remains uninvestigated. Therefore, we examined the effectiveness of nobiletin against cellular metastasis of human osteosarcoma and the underlying mechanisms. Nobiletin, up to 100 μM without cytotoxicity, significantly decreased motility, migration and invasion as well as enzymatic activities, protein levels and mRNA expressions of matrix metalloproteinase (MMP)-2 and MMP-9 in U2OS and HOS cells. In addition to inhibition of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), the inhibitory effect of nobiletin on the DNAbinding activity of the transcription factor nuclear factor-kappa B (NF-κB), cAMP response element-binding protein (CREB), and specificity protein 1 (SP-1) in U2OS and HOS cells. Co-treatment with ERK and JNK inhibitors and nobiletin further reduced U2OS cells migration and invasion. These results indicated that nobiletin inhibits human osteosarcoma U2OS and HOS cells motility, migration and invasion by downregulating MMP-2 and MMP-9 expressions via ERK and JNK pathways and through the inactivation of downstream NF-κB, CREB, and SP-1. Nobiletin has the potential to serve as an anti-metastatic agent for treating osteosarcoma.

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“…The MMP family comprises 24 zincdependent endopeptidases, and serves important roles in tumor metastasis and MMP26 is associated with the invasion and metastasis of non-small cell lung cancer (34)(35)(36). It has been reported that the expression of MMPs is regulated by MAPK pathways (37,38). To confirm whether ERK and p38 signaling pathway is involved in this situation, we applied specific inhibitors for ERK and p38, respectively, to the FGF18-stimulated H460 cells.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast growth factor 18 promotes proliferation and migration of H460 cells via the ERK and p38 signaling pathways

et al. 2016

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Abstract.Recently, fibroblast growth factor 18 (FGF18) expression was reported to be upregulated in colon cancer and ovarian cancer, and increased expression of FGF18 mRNA and protein is associated with tumor progression and poor overall survival in patients; however, its role in lung cancer remains to be explored. In the present study, the effect and underlying molecular mechanisms of FGF18 on H460 cells were investigated. Cell proliferation and cell cycle alterations were detected using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and flow cytometry. A wound healing assay was conducted to detect cell migration. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to measure extracellular signal-regulated kinase (ERK), p38 and matrix metalloproteinase 26 (MMP26) expression. Knockdown of FGF18 using short interfering RNA (siRNA-FGF18) suppressed H460 cell proliferation, inhibited cell migration via the downregulation of MMP26 levels, with siRNA-FGF18 additionally inhibiting the ERK and p38 signaling pathway. The present study indicates that FGF18 serves an essential role in the growth and migration of non-small cell lung cancer (NSCLC) cells by regulating the ERK, p38 signaling pathways and MMP26 protein levels, suggesting that FGF18 may be a potential molecular drug target for the treatment NSCLC.

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Chrysin Inhibits Tumor Promoter-Induced MMP-9 Expression by Blocking AP-1 via Suppression of ERK and JNK Pathways in Gastric Cancer Cells

Cited by 67 publications

References 37 publications

Improved chemotherapeutic efficacy of injectable chrysin encapsulated by copolymer nanoparticles

Improved chemotherapeutic efficacy of injectable chrysin encapsulated by copolymer nanoparticles

Nobiletin inhibits human osteosarcoma cells metastasis by blocking ERK and JNK-mediated MMPs expression

Fibroblast growth factor 18 promotes proliferation and migration of H460 cells via the ERK and p38 signaling pathways

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