<i>Gleditsia sinensis</i> thorn extract inhibits human colon cancer cells: the role of ERK1/2, G2/M‐phase cell cycle arrest and p53 expression

Lee, Se-Jung; Park, Keerang; Ha, Sandie; Kim, Wun-Jae; Moon, Sung‐Kwon

doi:10.1002/ptr.3214

Cited by 43 publications

(32 citation statements)

References 30 publications

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“…ERK, JNK and p38 MAPK constitute 3 major subfamilies of MAPKs that appear to mediate cellular responses, including proliferation, differentiation and apoptosis (30). Gleditsia sinensis thorns (WEGS) induced phosphorylation of ERK1/2, p38 MAPK and JNK in human colon cancer cells (31). Danshensu increased phosphorylation of Akt and ERK1/2 in H9c2 cardiomyocytes (32).…”

Section: Discussionmentioning

confidence: 99%

Triptolide induces apoptosis of PMA-treated THP-1 cells through activation of caspases, inhibition of NF-κB and activation of MAPKs

Park

Kim

2013

International Journal of Oncology

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Abstract.Triptolide is known to be involved in many cellular events, such as those related to immunosuppressive and antitumor activity. We investigated whether triptolide mediates these effects through multiple mechanisms, including activation of cell cycle arrest and caspase-dependent pathways, as well as by blocking nuclear factor-κB (NF-κB) activation and by potentiating the activities of the mitogen-activated protein kinase (MAPK) pathway, in phorbol myristate acetate (PMA)-differentiated THP-1 cells. Triptolide significantly inhibited cell proliferation in a dose-and time-dependent manner and it increased the apoptotic fraction in the cell cycle and the number of apoptotic THP-1 cells. Exposure of the cells to triptolide also increased caspase-3 activity in these cells. Furthermore, co-treatment of cells with triptolide and the pancaspase inhibitor, Z-VAD-FMK, or the caspase-3 inhibitor, Z-DEVE-FMK, increased THP-1 cell growth. Triptolide treatment resulted in a significant decrease in mRNA expression levels in genes encoding Bcl-2, cyclin D1, p27 and survivin and an increase in those encoding Bax and p21 in THP-1 cells. Triptolide not only inhibited NF-κB activation, but also activated p38 MAPK and MEK/ERK phosphorylation. These results show that triptolide inhibits the growth of THP-1 cells by inducing apoptosis through caspase activation and the mechanism involves NF-κB inhibition and the MAPK pathway.

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Section: Discussionmentioning

confidence: 99%

Triptolide induces apoptosis of PMA-treated THP-1 cells through activation of caspases, inhibition of NF-κB and activation of MAPKs

Park

Kim

2013

International Journal of Oncology

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“…Growth inhibition caused by ERK1/2 loss is rescued by reintroducing ERK2, but not by activating ERKs effectors that promote G1 cell cycle progression (38). Some natural compounds, such as oridonin (39) and Gleditsis sinensis thorn extract, reportedly induce G2/M arrest through ERK signaling (40). Our data showed that induction of cell cycle arrest by norathyriol may be mediated through ERKs signaling because norathyriol strongly suppresses ERK1 and 2 phosphorylation and kinase activities.…”

Section: Discussionmentioning

confidence: 99%

Norathyriol Suppresses Skin Cancers Induced by Solar Ultraviolet Radiation by Targeting ERK Kinases

Malakhova

Mottamal

et al. 2012

Cancer Research

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Ultraviolet (UV) irradiation is the most important factor contributing to the development of skin cancer. The use of chemopreventive agents, especially naturally occurring plant products, to prevent skin cancer caused by UV might an effective therapeutic or preventive intervention. Using in silico virtual screening of the Chinese Medicine Library, we identified norathyriol as a potential ERK2 inhibitor. Norathyriol is a metabolite of mangiferin, which is found in mango, Hypericum elegans, and Tripterospermum lanceolatum, and has potent anticancer-promoting activity. Here, we show that norathyriol inhibits ERK1/2 kinase activities and attenuates UVB-induced phosphorylation of the mitogen-activated protein kinase (MAPK) cascades. Direct binding of norathyriol with ERK2 was confirmed by a co-crystal structure. The norathyriol xanthone moiety acts as an adenine mimeric and anchors the compound by hydrogen bonds to the hinge region of the protein ATP-binding site. Norathyriol inhibited cell growth in mouse skin epidermal JB6 P+ cells by inducing G2-M phase arrest. Mouse skin tumorigenesis data clearly showed that treatment with norathyriol significantly suppressed solar UV-induced skin carcinogenesis in vivo. Results also indicated that norathyriol exhibits a potent chemopreventive activity through the inhibition of transcription factor AP-1 and NF-κB by targeting ERKs in UV-induced skin carcinogenesis.

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“…However, adverse effects of bevacizumab have been reported, such as hypertension, and there are a number of potential problems that warrant caution in human clinical trials [3,45]. Recently, several plant-derived compounds have been shown to be potent inhibitors of angiogenesis both in vitro and vivo [19,29,50]. Therefore, herbal medicine with few side effects is a promising strategy for anti-angiogenic tumor therapy.…”

Section: Introductionmentioning

confidence: 99%

The Anti-angiogenic Potential of a Phellodendron amurense Hot Water Extract in Vitro and ex Vivo

Kim¹,

Kim²,

Bae³

et al. 2015

Journal of Life Science

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Blocking new blood-vessel formation (angiogenesis) is now recognized as a useful approach to the therapeutic treatment of many solid tumors. The best validated approach to date is to target the vascular endothelial growth-factor (VEGF) pathway, a key regulator of angiogenesis. Many natural products and extracts that contain a variety of chemopreventive compounds have been shown to suppress the development of malignancies through their anti-angiogenic properties. Phellodendron amurense, which is widely used in Korean traditional medicine, has been shown to possess antitumor, antimicrobial, and anti-inflammatory properties, among others. The present study investigated the effects of P. amurense hot-water extract (PAHWE) on angiogenesis, a key process in tumor growth, invasion, and metastasis. To investigate PAHWE's anti-angiogenic properties, this study's authors performed an analysis of angiogenesis and endothelial-cell proliferation, migration, invasion, and tube formation, as well as zymogram assays and the rat aortic ring-sprouting assay. PAHWE inhibited cell growth, mobility, and vessel formation in response to VEGF in vitro and ex vivo. Furthermore, it reduced VEGF-induced intracellular signaling events, such as the activation of matrix metalloproteinases (MMPs) -2 and -9. These results indicate that PAHWE's anti-angiogenic properties might lead to the development of potential drugs for treating angiogenesis-associated diseases such as cancer.

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Gleditsia sinensis thorn extract inhibits human colon cancer cells: the role of ERK1/2, G2/M‐phase cell cycle arrest and p53 expression

Cited by 43 publications

References 30 publications

Triptolide induces apoptosis of PMA-treated THP-1 cells through activation of caspases, inhibition of NF-κB and activation of MAPKs

Triptolide induces apoptosis of PMA-treated THP-1 cells through activation of caspases, inhibition of NF-κB and activation of MAPKs

Norathyriol Suppresses Skin Cancers Induced by Solar Ultraviolet Radiation by Targeting ERK Kinases

The Anti-angiogenic Potential of a Phellodendron amurense Hot Water Extract in Vitro and ex Vivo

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