Phenoxodiol, an anticancer isoflavene, induces immunomodulatory effects <i>in vitro</i> and <i>in vivo</i>

Georgaki, Sylvianna; Skopeliti, Margarita; Tsiatas, Marinos; Nicolaou, Katerina; Ioannou, Kyriaki; Husband, Alan J.; Bamias, Aristotelis; Dimopoulos, Meletios Α.; Constantinou, Andreas I.; Tsitsilonis, Ourania E.

doi:10.1111/j.1582-4934.2009.00695.x

Cited by 27 publications

(18 citation statements)

References 25 publications

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“…PBMC were isolated from normal donors' peripheral blood as described previously (Georgaki et al ., ). PBMC (500 × 10 3 cells/mL), HeLa, MCF‐7, FM3 and HCT‐116 (20–25 × 10 3 cells/mL), were seeded in 96‐well U‐bottom plates (200 μL/well) (Costar) and incubated with the methanol extract (300 µg/mL) and compounds 1 (100 µg/mL), 2 , 7 , 12 and 14 (200 µg/mL) for 72 h. Compound 8 (200 µg/mL) was tested only on HeLa.…”

Section: Methodsmentioning

confidence: 97%

Polar Constituents of Marrubium thessalum Boiss. & Heldr. (Lamiaceae) and their Cytotoxic/Cytostatic Activity

Argyropoulou

Samara

Tsitsilonis

et al. 2012

Phytotherapy Research

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The methanol extract of the aerial parts of Marrubium thessalum Boiss. & Heldr. (Lamiaceae) afforded 30 phenolic metabolites, belonging to the classes of phenylethanoid glycosides, flavonoids and simple phenolic compounds. The crude methanol extract as well as the secondary metabolites were screened for their cytotoxic/cytostatic effects against four human cancer cell lines, specifically HeLa, MCF-7, FM3 and HCT-116 and demonstrated considerable cell growth-inhibitory activity. The differential cytotoxicity of the compounds implied possible structure-activity relationships. Selected compounds were evaluated for their toxicity against human peripheral blood mononuclear cells, where some of them showed marginal toxic effects. The results suggest that M. thessalum produces secondary metabolites that demonstrate selective anticancer activity concomitantly with reduced toxicity on lymphocytes. The structure of such compounds can eventually lead to the development of novel pharmaceutical agents.

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Section: Methodsmentioning

confidence: 97%

Polar Constituents of Marrubium thessalum Boiss. & Heldr. (Lamiaceae) and their Cytotoxic/Cytostatic Activity

Argyropoulou

Samara

Tsitsilonis

et al. 2012

Phytotherapy Research

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“…Cells in cultures were counted using an improved Neubauer hemocytometer. Cell proliferation was tested using the 3 H‐thymidine incorporation assay according to Georgaki et al 11 To block VEGFR‐2 activity, 1 μg/ml of neutralizing anti‐VEGFR‐2 mAb or normal mouse IgG 1 mAb as an isotype control (R&D Systems) was added in cultures on days 0, 1, 3 and every 3 days thereafter.…”

Section: Methodsmentioning

confidence: 99%

VEGF directly suppresses activation of T cells from ovarian cancer patients and healthy individuals via VEGF receptor Type 2

Ziogas

Gavalas

Tsiatas

et al. 2011

Intl Journal of Cancer

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142

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The role of vascular endothelial growth factor (VEGF) in tumor angiogenesis is well characterized; nevertheless, it is also a key element in promoting tumor evasion of the immune system by downregulating dendritic cell maturation and thus T cell activation. We sought to investigate the possible direct effect of VEGF on T cell activation and through which type of VEGF receptor (VEGFR) it exerts this effect. Circulating T cells from healthy donors and ovarian cancer patients were expanded in cultures with anti‐CD3 and IL‐2 with or without VEGF for 14 days, and the number of T cells was assessed. Cultured T cells were also tested for their cytotoxic activity in a standard 4‐hr 51Cr‐release assay, and the expression of VEGFRs 1, 2 and 3 was assayed by flow cytometry, immunocytochemistry and Western blotting. To assess the ability of activated T cells to secrete VEGF, levels in culture supernatants were measured by enzyme linked immunosorbent assay. The addition of VEGF in cultures significantly reduced T cell proliferation in a dose‐dependent manner. Protein expression studies demonstrated that CD3+ T cells express VEGFR‐2 on their surface upon activation. Experiments with anti‐VEGFR‐2 antibodies showed that the direct suppressive effect of VEGF on T cell proliferation is mediated by VEGFR‐2. We also showed that VEGF significantly reduced the cytotoxic activity of T cells and that activated T cells secrete VEGF in the culture environment. Overall, our study shows that T cells secret VEGF and expresses VEGFR‐2 upon activation. VEGF directly suppresses T cell activation via VEGF receptor type 2.

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“…Haginin E (Phenoxodiol) (254) development as an antitumor drug was based to a large extent on its low toxicity in normal tissues, but potent topoisomerase-II inhibitory effects in rapidly dividing tumor cells. This advantage led to its fast-track FDA approval for Phase II/ III clinical trials [125].…”

Section: Flavonoids -From Biosynthesis To Human Healthmentioning

confidence: 99%

Isoflavonoids

Foudah¹,

Abdel-Kader²

2017

Flavonoids - From Biosynthesis to Human Health

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Isoflavonoids are interesting class of natural products due to their positive effects on human health. Isoflavonoids include isoflavones, isoflavanones, isoflavans, rotenoids and pterocarpans. Although they are reported from many plant families, most isoflavonoids are produced by the subfamily Papilionaceae of the Fabaceae. Various chromatographic methods have been applied for the purification of isoflavonoids. Simple Ultra Violet (UV) absorption spectra as well as both One and two dimensional NMR (1D-and 2D-NMR) are critical for the identification of isoflavonoids. Each class of isoflavonoids has its unique feature in both 1 H-and 13 C-NMR that enable their proper characterization. High Resolution Mass Spectrometry (HRMS) is a substantial tool in such challenge. In vitro experiments indicated that isoflavonoids possess antioxidant, antimutagenic, antiproliferative as well as cancer preventive effects. Epidemiological studies provide support for some of these effects on human. Members of this class also are reported to have antimicrobial activity. In this chapter, isoflavones, isoflavanones, isoflavans, homoisoflavonoids and isoflavenes will be discussed in relation to their occurrence, methods of purification, spectral characters helpful in structure elucidation as well as their biological importance.

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Phenoxodiol, an anticancer isoflavene, induces immunomodulatory effects in vitro and in vivo

Cited by 27 publications

References 25 publications

Polar Constituents of Marrubium thessalum Boiss. & Heldr. (Lamiaceae) and their Cytotoxic/Cytostatic Activity

Polar Constituents of Marrubium thessalum Boiss. & Heldr. (Lamiaceae) and their Cytotoxic/Cytostatic Activity

VEGF directly suppresses activation of T cells from ovarian cancer patients and healthy individuals via VEGF receptor Type 2

Isoflavonoids

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