Endocrine Abstracts

Does the alkaloid sanguinarine inhibit VEGF transduction?

SE Santini, G Basini, S Bussolati & F Grasselli

Dipartimento di Produzioni Animali, Biotecnologie Veterinarie, Qualità e Sicurezza degli Alimenti. Sezione di Fisiologia Veterinaria, Parma, Italy.

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Angiogenesis has been shown to be fundamental for follicle development; Vascular Endothelial Growth Factor (VEGF), the major pro-angiogenetic factor, plays a critical role in the control of the follicular growth. Akt signalling is involved in VEGF transduction (Zachary, 2003) thus regulating multiple steps in angiogenesis. Sanguinarine (SA), an alkaloid isolated from Sanguinaria Canadensis, is known for its antiangiogenetic effects by suppressing basal and VEGF-induced new vessel growth (Eun and Koh, 2004). We previously documented (Bianco et al., 2005) that SA affects swine granulosa cells steroidogenic activity and inhibits VEGF production. The purpose of present study was to evaluate, in the same experimental model, possible effects of SA on Akt phosphorylation. Briefly, 10⁶ granulosa cells were collected from swine follicles >5 mm, seeded in 1 ml M199 and treated with: 1)VEGF (100 ng/ml); 2) SA (300 nM); 3) VEGF (100 ng/ml)+ SA (300 nM) at room temperature. After a 10 min incubation, Akt activity was evaluated by Akt/PKB Kinase Activity Assay Kit. VEGF treatment significantly (p<0.05) increased Akt activity in granulosa cells. SA alone was ineffective in modifying Akt activity, while this substance significantly (p<0.01) inhibited the VEGF-induced Akt increase. Since ovarian angiogenesis has been recognised as one of the key determinants of follicular development, our data suggest that SA may negatively affect female reproductive performance by blocking VEGF-induced Akt activation.

Acknowledgements: This work was supported by a FIL grant (University of Parma).

Bianco F, Basini G, & Grasselli F, The plant alkaloid Sanguinarine affects swine granulosa cell activity. Reprod Toxicol 2005 Submitted

Eun GP, & Koh GY, Suppression of angiogenesis by the plant alkaloid, sanguinarine. Biochem Biophys Res Commun 2004 317 618–624

Zachary I, VEGF signalling: integration and multi-tasking in endothelial cell biology. Biochem Soc Trans 2003 31 1171–1177

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Endocrine Abstracts (2005) 10 P67