Topotecan inhibits VEGF‐ and bFGF‐induced vascular endothelial cell migration via downregulation of the PI3K‐Akt signaling pathway

Nakashio, Ayako; Fujita, Naoya; Tsuruo, Takashi

doi:10.1002/ijc.10166

Cited by 90 publications

(66 citation statements)

References 23 publications

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“…Steinle et al (2002) proposed the signaling of endothelial cell proliferation by a PI3K/Akt/endothelial nitric-oxide synthase/protein kinase G/MAPK cascade. Nakashio et al (2002) found that PI3K-Akt was downregulated during topotecan-mediated inhibition of endothelial cell angiogenesis. Yao et al (2004) similarly demonstrated that minocycline exerted its inhibitory effect on angiogenesis by suppressing MMP-9 mRNA transcription and downregulating ERK1/2 and PI3K/ Akt signal pathways.…”

Section: Discussionmentioning

confidence: 98%

Radiation-enhanced hepatocellular carcinoma cell invasion with MMP-9 expression through PI3K/Akt/NF-κB signal transduction pathway

et al. 2006

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This study is to investigate the molecular mechanism of radiation-enhanced cell invasiveness of hepatocellular carcinoma (HCC) correlating with clinical patients undergoing radiotherapy and subsequently developing metastasis. Three HCC cell lines (HepG2, Hep3B and Huh7) and normal hepatocyte cell line (CL-48) were irradiated with different doses. The effect of radiation on cell invasiveness was determined using the Boyden chamber assay. Radiation-enhanced invasion capability was evident in HCC cells but not in normal hepatocytes. Invasion was observed in gelatin-coated but not fibronectin-coated or type I collagen-coated membranes. Radiation upregulated matrix metalloproteinase-9 (MMP-9) mRNA level, MMP-9 protein level and MMP-9 activity. MMP-9 antisense oligonucleotides inhibited radiation-induced MMP-9 expression and thereby significantly inhibited radiationinduced HCC invasion. Furthermore, phosphatidylinositol 3-kinase (PI3K)/Akt chemical inhibitors LY294002 and wortmannin suppressed radiation-induced MMP-9 mRNA expression. Transient transfection with dominantnegative Akt plasmid also showed that the PI3K/Aktsignaling pathway was involved in this radiation-induced MMP-9 expression. Moreover, nuclear factor-jB (NFjB) decoy oligodeoxynucleotide suppressed radiation enhanced MMP-9 promoter activity completely. PI3K/ Akt chemical inhibitors inhibited radiation-induced NFjB-driven luciferase promoter activity. Taken together, our results indicated that sublethal dose of radiation could enhance HCC cell invasiveness by MMP-9 expression through the PI3K/Akt/NF-jB signal transduction pathway.

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Section: Discussionmentioning

confidence: 98%

Radiation-enhanced hepatocellular carcinoma cell invasion with MMP-9 expression through PI3K/Akt/NF-κB signal transduction pathway

et al. 2006

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“…As a strong mitogenic factor and chemokine of vascular endothelial cells, bFGF is produced by paracrine and autocrine cells, and can combine with different receptors on the surface of vascular endothelial cells including TKR, heparan sulfate proteoglycan and cell adhesion molecules (CAMs) to activate their vasogenic characteristics (104,105). bFGF can also activate the P13K signaling pathway to inhibit apoptosis of vascular endothelial cells and promote angiogenesis (106). As a chemokine, bFGF can attract many kinds of vascular intimal cells by chemotaxis and induce them to produce proteolytic enzymes and collagenase which can promote the proliferation and migration of vascular endothelial cells as well as degrade extracellular matrix proteins to induce angiogenesis (107).…”

Section: The Relationship Between Fgf and Leukemiasmentioning

confidence: 99%

The progress of angiogenic factors in the development of leukemias

Han

Wang

et al. 2016

IRDR

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“…23,33,34) MAPK and PI3K/Akt pathways also play an important role in endothelial cell viability, migration, and tube formation by specific stimuli. [13][14][15]25,35,36) Therefore, we examined the effect of a-chaconine on the activities of MAPK and PI3K/Akt signaling pathways. Results demonstrated that treatment with a-chaconine inhibited JNK, PI3K and Akt phosphorylation significantly, suggesting that the signaling pathways mediated by JNK and PI3K/Akt were suppressed by a-chaconine.…”

Section: Fig 3 Effect Of A-chaconine On Chemotaxis and Invasion Of mentioning

confidence: 99%

.ALPHA.-Chaconine Inhibits Angiogenesis in Vitro by Reducing Matrix Metalloproteinase-2

Chen

Shih

et al. 2010

Biological & Pharmaceutical Bulletin

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Glycoalkaloids are the biologically active secondary metabolites found in many plants, such as potatoes. Glycoalkaloids are produced in leaves, roots, tubers and sprouts of the potato plant, and are involved in host plant resistance to bacteria, fungi, viruses, and insects. 1) Several reports have showed that glycoalkaloids suppress the growth of cancer cells in human skin, liver, prostate, breast and colon. 2-4) aChaconine, a trisaccharide glycoalkaloid, is the main steroidal glycoalkaloid in potato (Solanum tuberosum). 1) Recent studies demonstrated that a-chaconine inhibited the growth of human colon (HT29), liver (HepG2), cervical (HeLa), lymphoma (U937), and stomach (AGS and KATO III) cancer cells. 3,5) a-Chaconine also induced apoptosis of human colon cancer cells through the inhibition of extracellular signal regulating kinase (ERK) phosphorylation and activation of caspase-3. 6) In addition, a-chaconine inhibited migration and invasion of human lung adenocarcinoma A549 cells by reducing matrix metalloproteinase (MMP)-2 and MMP-9 activities through the suppression of phosphatidylinositide-3 kinase/ Akt/nuclear factor kappa B (PI3K/Akt/NF-kB) signaling pathway. 7) Therefore, a-chaconine may possess the potential for cancer chemotherapeutic action.Angiogenesis, a process of new blood vessel formation from a pre-existing microvascular network, plays important roles in many physiological functions including wound healing, embryonic development, and the normal menstrual cycle. Angiogenesis is also involved in pathological conditions, such as ischemia, atherosclerosis, arthritis and carcinogenesis. 8) During tumor development, newly generated vessels are necessary for supplying sufficient oxygen and nutrients to the growing tumor mass, and facilitating the metastatic spreading. 8,9) The process of angiogenesis includes proliferation, migration, invasion, as well as tube formation of endothelial cells. The process of angiogenesis is promoted by expressing and secreting various proteases that can degrade most extracellular matrix (ECM) components. 10) MMPs, a family of Zn-dependent endopeptidases, are the major proteases in angiogenesis and are closely correlated with invasive and metastatic potentials of cancer cells. 11) Several MMPs, such as MMP-2 and MT1-MMP, are produced by endothelial cells and contribute to the process of angiogenesis. 12) As well as MMPs, the mitogen-activated protein kinases family members (MAPK) are also known to mediate angiogenesis. MAPK family members participate in numerous signaling cascades that play important regulatory roles in cell growth, apoptosis, differentiation, and angiogenesis. The diverse MAPK members are activated in response to various extracellular stimuli and have distinct downstream targets, thus stimulating endothelial cell proliferation and protease production, and acting as positive mediators of angiogenesis. [13][14][15] Angiogenesis is also regulated by PI3K/Akt signaling pathway, which has been implicated in a number of cellular functions including cell survi...

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Topotecan inhibits VEGF‐ and bFGF‐induced vascular endothelial cell migration via downregulation of the PI3K‐Akt signaling pathway

Cited by 90 publications

References 23 publications

Radiation-enhanced hepatocellular carcinoma cell invasion with MMP-9 expression through PI3K/Akt/NF-κB signal transduction pathway

Radiation-enhanced hepatocellular carcinoma cell invasion with MMP-9 expression through PI3K/Akt/NF-κB signal transduction pathway

The progress of angiogenic factors in the development of leukemias

.ALPHA.-Chaconine Inhibits Angiogenesis in Vitro by Reducing Matrix Metalloproteinase-2

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