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Abstract Title:

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

Abstract Source:

Life Sci. 2009 Jun 19;84(25-26):915-22. Epub 2009 Apr 22. PMID: 19393247

Abstract Author(s):

Yen-Chun Chen, Chia-Ni Chang, Hui-Chun Hsu, Shu-Jiau Chiou, Lain-Tze Lee, Tzong-Hsiung Hseu

Article Affiliation:

Biomedical Engineering Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan. YenChunChen@itri.org.tw

Abstract:

AIMS: To address the possibility that sennoside B inhibition of cell proliferation is mediated via interference with platelet-derived growth factor (PDGF) signaling.

MAIN METHODS: Human osteosarcoma MG63 cells were treated with PDGF in the presence or absence of sennoside B. Activation of the PDGF signaling pathway was monitored using western immunoblotting with specific antibodies against the PDGF receptor, phosphotyrosine and components of the downstream signaling cascade. Activation of cell metabolism and proliferation was assessed by chromogenic reduction of MTT.

KEY FINDINGS: Sennoside B was found to inhibit PDGF-BB-induced phosphorylation of the PDGF receptor (PDGFR) in human MG63 osteosarcoma cells. Downstream signaling was also affected; pre-incubation of PDGF-BB with sennoside B inhibited the phosphorylation of pathway components including Ak strain transforming protein (AKT), signal transducer and activator of transcription 5 (STAT-5) and extracellular signal-regulated kinase 1/2 (ERK1/2). Further, we found that sennoside B can bind directly to the extracellular domains of both PDGF-BB and the PDGF-beta receptor (PDGFR-beta). The effect was specific for sennoside B; other similar compounds including aloe-emodin, rhein and the meso isomer (sennoside A) failed to inhibit PDGFR activation or downstream signaling. Sennoside B also inhibited PDGF-BB stimulation of MG63 cell proliferation.

SIGNIFICANCE: These results indicate that sennoside B can inhibit PDGF-stimulated cell proliferation by binding to PDGF-BB and its receptor and by down-regulating the PDGFR-beta signaling pathway. Sennoside B is therefore of potential utility in the treatment of proliferative diseases in which PDGF signaling plays a central role.

Study Type : In Vitro Study
Additional Links
Pharmacological Actions : Antiproliferative : CK(4773) : AC(3450)

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Sayer Ji
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