Wogonin preferentially kills malignant lymphocytes and suppresses T-cell tumor growth by inducing PLCgamma1- and Ca2+-dependent apoptosis.
Blood
; 111(4): 2354-63, 2008 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-18070986
ABSTRACT
Herbs have successfully been used in traditional Chinese medicine for centuries. However, their curative mechanisms remain largely unknown. In this study, we show that Wogonin, derived from the traditional Chinese medicine Huang-Qin (Scutellaria baicalensis Georgi), induces apoptosis in malignant T cells in vitro and suppresses growth of human T-cell leukemia xenografts in vivo. Importantly, Wogonin shows almost no toxicity on T lymphocytes from healthy donors. Wogonin induces prolonged activation of PLCgamma1 via H(2)O(2) signaling in malignant T cells, which leads to sustained elevation of cytosolic Ca(2+) in malignant but not normal T cells. Subsequently, a Ca(2+) overload leads to disruption of the mitochondrial membrane. The selective effect of Wogonin is due to its differential regulation of the redox status of malignant versus normal T cells. In addition, we show that the L-type voltage-dependent Ca(2+) channels are involved in the intracellular Ca(2+) mobilization in T cells. Furthermore, we show that malignant T cells possess elevated amounts of voltage-dependent Ca(2+) channels compared with normal T cells, which further enhance the cytotoxicity of Wogonin for malignant T cells. Taken together, our data show a therapeutic potential of Wogonin for the treatment of hematologic malignancies.
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Base de dados:
MEDLINE
Assunto principal:
Leucemia de Células T
/
Cálcio
/
Apoptose
/
Flavanonas
/
Fosfolipase C gama
Limite:
Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article