Sennoside B inhibits PDGF receptor signaling and cell proliferation induced by PDGF-BB in human osteosarcoma cells

Chen, Yen-Chun; Chang, Chih Ming; Hsu, Hui‐Chun; Chiou, Shu-Jiau; Lee, Lain-Tze; Hseu, Tzong-Hsiung

doi:10.1016/j.lfs.2009.04.003

Cited by 22 publications

(21 citation statements)

References 26 publications

(25 reference statements)

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“…Upregulation of the PDGFB pathway has been demonstrated in canine hemangiosarcoma, feline injection site sarcoma, 3,28 and human sarcomas, 32 in which it has been also targeted for therapeutic purposes. 9,12 The bFGF-Flg pathway was also highly expressed by canine PWTs. bFGF is a potent angiogenic factor that stimulates EC and MC proliferation.…”

Section: Discussionmentioning

confidence: 99%

Growth Factors and COX2 Expression in Canine Perivascular Wall Tumors

et al. 2015

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Canine perivascular wall tumors (PWTs) are a group of subcutaneous soft tissue sarcomas developing from vascular mural cells. Mural cells are involved in angiogenesis through a complex crosstalk with endothelial cells mediated by several growth factors and their receptors. The evaluation of their expression may have relevance since they may represent a therapeutic target in the control of canine PWTs. The expression of vascular endothelial growth factor (VEGF) and receptors VEGFR-I/II, basic fibroblast growth factor (bFGF) and receptor Flg, platelet-derived growth factor B (PDGFB) and receptor PDGFRb, transforming growth factor b1 (TGFb1) and receptors TGFbR-I/II, and cyclooxygenase 2 (COX2) was evaluated on frozen sections of 40 PWTs by immunohistochemistry and semiquantitatively scored to identify their potential role in PWT development. Statistical analysis was performed to analyze possible correlations between Ki67 labeling index and the expression of each molecule. Proteins of the VEGF-, PDGFB-, and bFGF-mediated pathways were highly expressed in 27 (67.5%), 30 (75%), and 19 (47.5%) of 40 PWTs, respectively. Proteins of the TGFb1-and COX2-mediated pathways were highly expressed in 4 (10%) and 14 (35%) of 40 cases. Statistical analysis identified an association between VEGF and VEGFR-I/II (P ¼ .015 and .003, respectively), bFGF and Flg (P ¼ .038), bFGF and PDGFRb (P ¼ .003), and between TGFb1 and COX2 (P ¼ .006). These findings were consistent with the mechanisms that have been reported to play a role in angiogenesis and in tumor development. No association with Ki67 labeling index was found. VEGF-, PDGFB-, and bFGF-mediated pathways seem to have a key role in PWT development and growth. Blockade of tyrosine kinase receptors after surgery could represent a promising therapy with the aim to reduce the PWT relapse rate and prolong the time to relapse.

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Section: Discussionmentioning

confidence: 99%

Growth Factors and COX2 Expression in Canine Perivascular Wall Tumors

et al. 2015

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“…Understanding how sennoside B affects the mucosal intestinal immune system could provide important clues to the SR-A pathway and the biological implications of this drug as an immunomodulatory compound. In addition, sennoside B has been demonstrated to inhibit PDGF receptor signaling and cell proliferation induced by PDGF-BB in human osteosarcoma cells (27).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Antigen Trafficking through Scavenger Receptor A

Raycroft

Harvey

Bruck

et al. 2012

Journal of Biological Chemistry

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Background: Scavenger receptor A (SR-A) is implicated in the development of autoimmunity. Results: Deficiency of SR-A, anti-SR-A antibody, and small molecule inhibitors (SMIs) block antigen processing. Conclusion: Two SMIs (sennoside B and tannic acid) that reduce antigen transfer and T cell immunity were identified. Significance: SR-A-mediated antigen trafficking is blocked by SMIs, leading to reduced T cell responses.

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“…Numerous studies have reported that the c-Jun N-terminal kinases (JNK), p38 and extracellular signal-regulated kinases (ERK1/2) cascades exert a vital role in regulating cytotoxic drug induced apoptosis in OS (18,19). Thus, targeting the pathway may have clinical value in the treatment of OS.…”

Section: Cucurbitacin B Inhibits Cell Proliferation and Induces Apoptmentioning

confidence: 99%

“…Researchers have reported that cucurbitacin I may inhibit cancer cell growth by disrupting the JAK/STAT3 signaling pathway in both in vitro and in vivo tumor models (29,30). Studies have reported that cucurbitacin B inhibits the growth of various human cancer cell lines and tumor xenografts including breast, prostate, lung, uterine cervix, liver, skin and brain cancer (18,31,32). Considering the biological effects cucurbitacin B, the present study aimed investigate the effects of cucurbitacin B on human OS cells and assess whether it modulates the JAK/STAT3 and MAPK signalling pathways.…”

Section: Cucurbitacin B Inhibits Cell Proliferation and Induces Apoptmentioning

confidence: 99%

Cucurbitacin B inhibits cell proliferation and induces apoptosis in human osteosarcoma cells via modulation of the JAK2/STAT3 and MAPK pathways

Zhang

Gao

Yang

2017

Experimental and Therapeutic Medicine

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Abstract. Osteosarcoma (OS) is the most commonly diagnosed tumor of the bones in children and young adults. Even with conventional therapies the 5-year survival rate is ~65% in patients with OS. Considering the side effects and aggressiveness of malignant bone tumors, research is focussing on multi-targeted strategies in treatment. Cucurbitacin B, a triterpenoid compound has been demonstrated to induce apoptosis in various cancer cell types. The Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signalling cascades and mitogen activated protein kinases (MAPK) signalling cascades are critical regulators of tumorigenesis. The present study assessed the influence of cucurbitacin B on the viability and expression of MAPKs and proteins of the JAK2/STAT3 cascades in human OS cells (U-2 OS). Cucurbitacin B (20-100 µM) significantly reduced cell viability (P<0.05) and induced apoptosis, as assessed by MTT and Annexin V/propidium iodide staining, along with inhibiting cell migration. Gelatin zymography revealed supressed activities of matrix metalloproteinase (MMP-)2 and 9. Furthermore, cucurbitacin B effectively upregulated the apoptotic pathway and caused the effective inhibition of MAPK signalling and JAK2/STAT3 cascades. Multifold suppression of vascular endothelial growth factor by cucurbitacin B was also observed, indicating inhibition of angiogenesis. Thus, by downregulating major pathways-MAPK and JAK2/STAT3 and MMPs, cucurbitacin B has potent anti-proliferative and anti-metastatic effects that require further investigation with regards to cancer treatment.

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Sennoside B inhibits PDGF receptor signaling and cell proliferation induced by PDGF-BB in human osteosarcoma cells

Cited by 22 publications

References 26 publications

Growth Factors and COX2 Expression in Canine Perivascular Wall Tumors

Growth Factors and COX2 Expression in Canine Perivascular Wall Tumors

Inhibition of Antigen Trafficking through Scavenger Receptor A

Cucurbitacin B inhibits cell proliferation and induces apoptosis in human osteosarcoma cells via modulation of the JAK2/STAT3 and MAPK pathways

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