Regulatory Effects of Siegesbeckia glabrescens on Non-Small Cell Lung Cancer Cell Proliferation and Invasion

J Cellular Molecular Medi

Ahn

et al. 2020

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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.

Section: Methodsmentioning

confidence: 99%

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

J Cellular Molecular Medi

Ahn

et al. 2020

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“…Cells were rinsed twice with ice-cold PBS and lysed by incubation in 50 mM Tris-HCl (pH 7.4), 150 mM NaCl, 10% glycerol, 1% Triton X-100, 1 mM EDTA, 100 µg/ml 4-(2-aminoethyl)benzenesulfonyl fluoride, 10 µg/ml aprotinin, 1 µg/ml pepstatin A, 0.5 µg/ml leupeptin, 80 mM β-glycerophosphate, 25 mM sodium fluoride and 1 mM sodium orthovanadate for 30 min at 4˚C. Cell lysates were clarified at 12,500 x g for 20 min at 4˚C and the supernatants were subjected to western blot analysis as described previously (36)(37)(38). All western blot analyses are representative of at least three independent experiments.…”

Section: Methodsmentioning

confidence: 99%

Ligularia fischeri inhibits endothelial cell proliferation, invasion and tube formation through the inactivation of mitogenic signaling pathways and regulation of vascular endothelial cadherin distribution and matrix metalloproteinase expression

et al. 2015

Oncology Reports

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Abstract. Ligularia fischeri (LF) has been used as an edible herb and traditional medicine for the treatment of inflammatory and infectious diseases. In the present study, we report the effects and molecular mechanism of the ethanolic extract of LF on cell proliferation, invasion and tube formation in human umbilical vein endothelial cells (HUVECs). LF-mediated inhibition of cell proliferation was accompanied by reduced expression of cell cycle-related proteins such as cyclin-dependent kinases (Cdks) and cyclins, leading to pRb hypophosphorylation and G 1 phase cell cycle arrest. We also show that LF treatment inhibited cell invasion and tube formation in HUVECs. These anti-angiogenic activities of LF were associated with the inactivation of mitogenic signaling pathways, induction of vascular endothelial (VE)-cadherin distribution at cell-cell contacts and inhibition of matrix metalloproteinase (MMP) expression. Collectively, our findings demonstrate the pharmacological functions and molecular mechanisms of LF in regulating endothelial cell fates, and support further development as a potential therapeutic agent for the treatment and prevention of angiogenesis-related disorders including cancer. IntroductionAngiogenesis, the formation of new blood vessels from pre-existing neighboring vessels, is essential for pathological conditions including cancer, ocular disorders, arthritis and obesity as well as physiological processes such as wound-healing, menstruation and ovulation (1,2). The process of angiogenesis includes endothelial cell proliferation, migration, adhesion, invasion, tube formation and recruitment of pericytes, and is tightly regulated by the complex interplay of angiogenic and anti-angiogenic factors within tissue microenvironment (3-5). Matrix metalloproteinases (MMPs) play important roles in tissue remodeling by degrading extracellular matrix (ECM) components and cell surface molecules, leading to angiogenic responses associated with cancer growth and progression (6-8). MMP-mediated cleavage of vascular endothelial (VE)-cadherin in cell surfaces may promote vascular permeability, proliferation, invasion and capillary-like structure formation by dissociating cadherin-catenin complex and disrupting cell-cell adhesion (9-14). The activities of these MMPs are regulated by endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs) (15). In addition to MMP-inhibitory activity, many investigations demonstrate that TIMPs regulate cell fates such as proliferation, migration, apoptosis and differentiation through MMP-independent mechanism (16)(17)(18)(19)(20)(21)

“…After serum starvation for 2 h, the cells were pretreated with marmesin (10 µM) for 30 min, followed by 10% FBS stimulation for 16 h. The inserts were fixed with methanol and using a cotton-tipped swab the non-invasive cells were removed from the top of the membrane. After staining with 0.04% Giemsa staining solution (Sigma-Aldrich Co., St. Louis, MO, USA), the numbers of invasive cells (mean ± standard deviation) were determined from six different fields using x200 objective magnification (21,22).…”

Section: Marmesin-mediated Suppression Of Vegf/vegfr and Integrin β1 mentioning

confidence: 99%

Marmesin-mediated suppression of VEGF/VEGFR and integrin β1 expression: Its implication in non-small cell lung cancer cell responses and tumor angiogenesis

Lee

et al. 2016

Oncology Reports

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In the present study, we investigated the effects and molecular mechanism of marmesin, a natural coumarin compound isolated from Broussonetia kazinoki, on non-small cell lung cancer (NSCLC) cell responses and tumor angiogenesis. Marmesin abrogated mitogen-stimulated proliferation and invasion in both p53 wild-type A549 and p53-deficient H1299 NSCLC cells. These antitumor activities of marmesin were mediated by the inactivation of mitogenic signaling pathways and downregulation of cell signaling-related proteins including vascular endothelial growth factor receptor-2 (VEGFR-2), integrin β1, integrin-linked kinase and matrix metalloproteinases-2. Furthermore, marmesin suppressed the expression and secretion of VEGF in both NSCLC cells, leading to inhibition of capillary-like structure formation in human umbilical vein endothelial cells. Collectively, these findings demonstrate the pharmacological roles and molecular targets of marmesin in regulating NSCLC cell responses and tumor angiogenesis.