Anti-angiogenic effects of Siegesbeckia glabrescens are mediated by suppression of the Akt and p70S6K-dependent signaling pathways

Kim, Hyeon-Ju; Ko, Hee-Young; Choi, Seoyeon; Seo, Dong Wan

doi:10.3892/or.2014.3630

Cited by 12 publications

(8 citation statements)

References 31 publications

(29 reference statements)

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“…ERK signalling has been reported to not only participate in various tumor transitions for cell survival and invasion [ 42 , 43 ] but also modulate the transcription factors for tumor EMT and angiogenesis [ 44 , 45 ]. P70S6K is one of the ERK pathway effectors, and an increasing amount of evidence demonstrates that ERK/p70S6K signalling participates in several pathological processes, such as cell drug-resistance and angiogenesis [ 46 , 47 ]. In addition, p70S6K modulates the expression and activation of HIF-1α [ 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA UBE2CP3 enhances HCC cell secretion of VEGFA and promotes angiogenesis by activating ERK1/2/HIF-1α/VEGFA signalling in hepatocellular carcinoma

Lin

Cao

Wang

et al. 2018

J Exp Clin Cancer Res

105

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BackgroundAngiogenesis is considered as an important process in the development of malignancies and is associated with cancer progression and metastasis. Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and is recognized as a typical angiogenic tumor. Thus, it is of great importance to study the underlying mechanism of angiogenesis in HCC. The long non-coding RNA (lncRNA) ubiquitin conjugating enzyme E2C pseudogene 3 (UBE2CP3) has been reported as an oncogene that promotes tumor metastasis in HCC. However, the role and underlying mechanisms of UBE2CP3 in HCC angiogenesis are still unclear.MethodsWe measured the expression levels of UBE2CP3 by in situ hybridization (ISH) and quantitative real-time polymerase chain reaction (qRT-PCR) in HCC patient samples. We also concomitantly used CD31/PAS double-staining to measure endothelial vessel (EV) density and used qRT-PCR to measure the CD31 mRNA level. HepG2 and SMMC-7721 cells were transfected with Lv-UBE2CP3 or Sh-UBE2CP3 virus to obtain stably over-expressing or knocking-down UBE2CP3 cell lines. The indirect effects of UBE2CP3 on ECs were studied by establishing a co-culture system using Transwell chambers with a 0.4-μm pore size. HCC cells and ECs in the co-culture system were separated, but the cytokines and growth factors were able to communicate with each other. Following exposed to HCC cells, ECs were collected for functional studies. Finally, we studied the function of UBE2CP3 in vivo by chick embryo chorioallantoic membrane (CAM) angiogenesis assays and nude mouse tumorigenicity assays.ResultsIn this study, we found that UBE2CP3 expression was higher in HCC tissues than in para-tumor tissues and was up-regulated in tissues with high EV density. Functionally, we found that in the co-culture systems, HCC cells overexpressing UBE2CP3 promoted HUVEC proliferation, migration and tube formation via the activation of ERK/HIF-1α/p70S6K/VEGFA signalling, increasing the level of VEGFA in HCC cell supernatant. In addition, the opposite results appeared when the expression of UBE2CP3 in HCC cells was knocked down. Consistent with these results, CAM angiogenesis assays and nude mouse tumorigenicity assays showed that UBE2CP3 expression up-regulated EV density in vivo.ConclusionOur study suggests that UBE2CP3 can enhance the interaction between HCC tumor cells and HUVECs and promote HCC tumorigenicity by facilitating angiogenesis.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0727-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Long non-coding RNA UBE2CP3 enhances HCC cell secretion of VEGFA and promotes angiogenesis by activating ERK1/2/HIF-1α/VEGFA signalling in hepatocellular carcinoma

Lin

Cao

Wang

et al. 2018

J Exp Clin Cancer Res

105

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“…In the present study, we investigated the regulatory effects and signaling pathways of 10-gingerol on cell proliferation and invasion in MDA-MB-231 breast cancer cells. or SB203580 (5 μM) for 30 min, and further incubated with 10% FBS for 24 h. Following culture for 24 h, the number of cells was quantified using trypan blue exclusion method as described previously (23,24). The results from triplicate determinations (mean ± standard deviation) are presented as the fold-increase of untreated controls.…”

Section: Introductionmentioning

confidence: 99%

10-Gingerol inhibits proliferation and invasion of MDA-MB-231 breast cancer cells through suppression of Akt and p38MAPK activity

et al. 2015

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In the present study, we investigated the roles and molecular mechanism of 10-gingerol, a phenolic compound isolated from Zingiber officinale, in regulating cell proliferation and invasion of MDA‑MB‑231 breast cancer cells. 10-gingerol treatment inhibited cell proliferation through downregulation of cell cycle regulatory proteins such as cyclin-dependent kinases and cyclins, and subsequent induction of G1 phase arrest. In addition, 10‑gingerol treatment blocked cell invasion in response to mitogenic stimulation. These antitumor activities of 10‑gingerol were mediated through inactivation of Akt and p38MAPK activity, and suppression of epidermal growth factor receptor expression. Collectively, these findings demonstrate the pharmacological roles of 10-gingerol in regulating breast cancer cell growth and progression, and suggest further evaluation and development as a potential therapeutic agent for the prevention and treatment of breast cancer.

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“…Cells were photographed and counted. The results (mean ± standard deviation) are presented as the numbers of adherent cells …”

Section: Methodsmentioning

confidence: 99%

Novel functions for 2‐phenylbenzimidazole‐5‐sulphonic acid: Inhibition of ovarian cancer cell responses and tumour angiogenesis

Kim

Ahn

et al. 2020

J Cellular Molecular Medi

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In this study, we investigated the effects and molecular mechanisms of 2‐phenylbenzimidazole‐5‐sulphonic acid (PBSA), an ultraviolet B protecting agent used in sunscreen lotions and moisturizers, on ovarian cancer cell responses and tumour angiogenesis. PBSA treatment markedly blocked mitogen‐induced invasion through down‐regulation of matrix metalloproteinase (MMP) expression and activity in ovarian cancer SKOV‐3 cells. In addition, PBSA inhibited mitogen‐induced cell proliferation by suppression of cyclin‐dependent kinases (Cdks), but not cyclins, leading to pRb hypophosphorylation and G1 phase cell cycle arrest. These anti‐cancer activities of PBSA in ovarian cancer cell invasion and proliferation were mediated by the inhibition of mitogen‐activated protein kinase kinase 3/6‐p38 mitogen‐activated protein kinase (MKK3/6‐p38MAPK) activity and subsequent down‐regulation of MMP‐2, MMP‐9, Cdk4, Cdk2 and integrin β1, as evidenced by treatment with p38MAPK inhibitor SB203580. Furthermore, PBSA suppressed the expression and secretion of vascular endothelial growth factor in SKOV‐3 cells, leading to inhibition of capillary‐like tubular structures in vitro and angiogenic sprouting ex vivo. Taken together, our results demonstrate the pharmacological effects and molecular targets of PBSA on modulating ovarian cancer cell responses and tumour angiogenesis, and suggest further evaluation and development of PBSA as a promising chemotherapeutic agent for the treatment of ovarian cancer.

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Anti-angiogenic effects of Siegesbeckia glabrescens are mediated by suppression of the Akt and p70S6K-dependent signaling pathways

Cited by 12 publications

References 31 publications

Long non-coding RNA UBE2CP3 enhances HCC cell secretion of VEGFA and promotes angiogenesis by activating ERK1/2/HIF-1α/VEGFA signalling in hepatocellular carcinoma

Long non-coding RNA UBE2CP3 enhances HCC cell secretion of VEGFA and promotes angiogenesis by activating ERK1/2/HIF-1α/VEGFA signalling in hepatocellular carcinoma

10-Gingerol inhibits proliferation and invasion of MDA-MB-231 breast cancer cells through suppression of Akt and p38MAPK activity

Novel functions for 2‐phenylbenzimidazole‐5‐sulphonic acid: Inhibition of ovarian cancer cell responses and tumour angiogenesis

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