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01.05.2012 | Original article

Scutellaria extract and wogonin inhibit tumor-mediated induction of T_reg cells via inhibition of TGF-β1 activity

verfasst von: Sagar Dandawate, Linford Williams, Nirmal Joshee, Agnes M. Rimando, Sandeep Mittal, Archana Thakur, Lawrence G. Lum, Prahlad Parajuli

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 5/2012

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Abstract

A number of studies have implicated tumor-induced T_reg cell activity in the sub-optimal response to therapeutic vaccines. Development of neo-adjuvant strategies targeting T_reg cells is therefore imperative. Scutellaria extracts or constituent flavonoids have shown encouraging efficacy against various tumors, including gliomas, in both pre-clinical and clinical studies. We report here, for the first time, that Scutellaria ocmulgee leaf extract (SocL) and flavonoid wogonin could inhibit TGF-β1-induced T_reg activity in malignant gliomas. F344 rats, subcutaneously transplanted with F98 gliomas, were treated with SocL. There was a significant inhibition of intra-tumoral TGF-β1 and T_reg cell frequency as well as peripheral blood TGF-β1 levels in SocL-treated animals compared to the controls. SocL extract and wogonin also inhibited glioma-induced, TGF-β1-mediated T_reg activity in vitro. SocL extract and wogonin also inhibited the secretion of IL-10 in T_reg culture; whereas the level of IL-2 was either unchanged or marginally enhanced. We also observed an inhibition of Smad-3, GSK-3β and ERK1/2 signaling by SocL and wogonin in T_reg cells, while phosphorylation of P38 MAPK was considerably enhanced, indicating that SocL or wogonin could inhibit the T cells’ response to TGF-β1 via modulation of both Smad and non-Smad signaling pathways. Overall, this study suggests that Scutellaria can potentially reverse tumor-mediated immune suppression via inhibition of TGF-β1 secretion as well as via inhibition of T cells’ response to TGF-β1. This may provide an opportunity for developing a novel adjuvant therapeutic strategy for malignant gliomas, combining Scutellaria with immunotherapy and chemo/radio-therapeutic regimen, which could potentially improve the disease outcome.

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Titel: Scutellaria extract and wogonin inhibit tumor-mediated induction of Treg cells via inhibition of TGF-β1 activity
verfasst von: Sagar Dandawate
Linford Williams
Nirmal Joshee
Agnes M. Rimando
Sandeep Mittal
Archana Thakur
Lawrence G. Lum
Prahlad Parajuli
Publikationsdatum: 01.05.2012
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 5/2012
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-011-1130-3

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