Flavonoids inhibit angiogenic cytokine production by human glioma cells

Abstract

VEGF and TGF-β1 are cytokines that stimulate tissue invasion and angiogenesis. These factors are considered as molecular targets for the therapy of glioblastoma. Bevacizumab, a recombinant humanized monoclonal antibody developed against VEGF, inhibits endothelial cell proliferation and vessel formation. Flavonoids obtained from Dimorphandra mollis and Croton betulaster have been described as proliferation inhibitors of a human glioblastoma derived cell line. VEGF and TGF-β1 levels were dosed by ELISA in a GL-15 cell line treated with bevacizumab and also with the flavonoids rutin, 5-hydroxy-7,4'-dimethoxyflavone, casticin, apigenin and penduletin. Rutin reduced the VEGF and TGF-β1 levels after 24 h but not after 72 h. The other flavonoids significantly reduced TGF-β1 production. Bevacizumab reduced only the VEGF levels in the supernatant from GL-15 cultures. These results suggest that the flavonoids studied, and commonly used in popular medicine, present an interesting subject of study due to their potential effect as angiogenic factor inhibitors.

Casticin inhibits COX-2 and iNOS expression via suppression of NF-κB and MAPK signaling in lipopolysaccharide-stimulated mouse macrophages

“…Recent studies found that casticin can inhibit intercellular adhesion molecule-1 (ICAM-1) expression and eosinophil migration in lung epithelial cells (Koh et al, 2011). Casticin can also induce apoptosis of cancer cells, including glioma cells, human lung cancer cells, cervical cancer cells, gastric cancer cells, and hepatocellular carcinomas (Freitas et al, 2011;Koh et al, 2011;Zhou et al, 2013). However, the anti-inflammatory effect of casticin is not fully understood.…”

Aqueous extract of Vitex trifolia L. (Labiatae) inhibits LPS-dependent regulation of inflammatory mediators in RAW 264.7 macrophages through inhibition of Nuclear Factor kappa B translocation and expression

“…Interestingly, luteolin inhibited the proliferation of a human myeloid leukaemia cell line and a human colon carcinoma cell lines by inducing apoptosis (Ko et al, 2002;Imai et al, 2009). Moreover, vitexicarpin showed the ability to reduce the production of the angiogenic Transforming Growth Factor (TGF)-b-1 by a human glioblastoma-derived cell line, emphazing its potential activity as angiogenic factors inhibitor (Freitas et al, 2011).…”

Molecular Mechanisms of Casticin Action: an Update on its Antitumor Functions

“…As shown in Figure 1, accumulated data indicate that casticin was isolated from many plant species such as, namely Vitex agnus castus (Choudhary et al, 2009;Mesaik et al, 2009;Webster et al, 2011;Righeschi et al, 2012;Hogner et al, 2013), Daphne genkwa (Xie et al, 2011), Achillea millefolium (Haidara et al, 2006;Csupor-Loffler et al, 2009), Ficus microcarpa , Vitex rotundifolia (Ono et al, 2002;Hu et al, 2007b;Shen et al, 2009;Ye et al, 2010;Koh et al, 2011), Fructus viticis (Hu et al, 2007b;Guan et al, 2010;Chen et al, 2011b;Yang et al, 2011;Zeng et al, 2012;Zhou et al, 2013a), Vitex negundo (Diaz et al, 2003;Kunwar et al, 2010;Velpandian et al, 2013), Crataegus pinnatifida (Kao et al, 2005), Pavetta crassipes (Mali and Dhake, 2011), Nelsonia canescens, Butea frondosa Koen , Dalbergia odorifera (Mali and Dhake, 2011), Bryonia laciniosa (Aggarwal et al, 2011), Citrus unshu (Mali and Dhake, 2011;Nagoor et al, 2011), Centipeda minima (Mali and Dhake, 2011), Clausena excavate (Manosroi et al, 2005), Croton betulaster (de Sampaio e Spohr et al, 2010;Freitas et al, 2011), Dimorphandra mollis (Freitas et al, 2011), Artemisia abrotanum L. (Hernandez et al, 1999), Artemisia annua L …”

“…Casticin induced early or late apoptosis in a dose dependent manner. Sub-G1 accumulation is usually considered as an apoptotic death profile, this evidence is in sync with mode of cell death and characterized by a set of physiological phenomena, including mitotic catastrophe (Ono et al, 2002;Hu et al, 2007a;Hu et al, 2007b;Shen et al, 2009;Guan et al, 2010;Ye et al, 2010;Chen et al, 2011a;Koh et al, 2011;Zeng et al, 2012;Zhou et al, 2013a) Fructus viticis Chaste tree Mang Jing Zi Fruit Anticancer, inflammation (Hu et al, 2007b;Guan et al, 2010;Chen et al, 2011a;Zeng et al, 2012;Zhou et al, 2013a) Dimorphandra mollis --------Seeds vascular disorders; hypertension (Freitas et al, 2011) Artemisia abrotanum L.…”

“…Furthermore, striking apoptosis was also confirmed in human glioma cells, accompanied by the up-regulation of caspase-3, p53 and pro-apoptotic protein Bax. These effects were absent when the caspase inhibitor z-VAD- KIP1 #, DR5# (Yang et al, 2011;He et al, 2013) Glioma U251, GL-15, U87, U373 50-100 µM p53#, Bax#, Caspace-3# (Freitas et al, 2011;Feng et al, 2012;Liu et al, 2013) Leukemia CCRF-CEM; CEM/ADR5000, K562, Kasumi-1, HL-60 fmk or p53 inhibitor PFTα were applied, suggesting that casticin could trigger cell apoptosis in a caspase-3 and p53-dependent manner (Liu et al, 2013). Accumulated data support that casticin can induces in p53-dependent and -independent manner in various cancer cells.…”