Huang-Qin (Wogonin) Sensitizes Cancer Cells to Apoptosis

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Blood First Edition Paper, prepublished online August 24, 2006

Submitted March 23, 2006

Accepted July 24, 2006

Wogonin sensitizes resistant malignant cells to TNF{alpha}- and

TRAIL-induced apoptosis

Stefanie C Fas, Sven Baumann, Jia Yun Zhu, Marco Giaisi, Monika K

Treiber, Ulrich Mahlknecht, H Krammer, and Min Li-Weber*

Tumorimmunology Program, German Cancer Research Center, Heidelberg,

Germany

German Cancer Research Center D030

Department of Hematology/Oncology, University of Heidelberg Medical

Center, Heidelberg, Germany

TNF{alpha} has previously been used in anti-cancer therapy. However,

the therapeutic application of TNF{alpha} was largely limited due to

its general toxicity and the fact that it activates the

NF-{kappa}B-family transcription factors which are pro-inflammatory

and anti-apoptotic.

To overcome this problem in vitro, specific NF-{kappa}B inhibitors,

transcription or protein synthesis inhibitors such as actinomycin D

and cycloheximide are usually used in combination to increase

TNF{alpha}-killing of tumor cells. However, these agents also cause

harmful side effects in vivo.

We show here that wogonin, derived from the popular Chinese herb

Huang-Qin, attenuates NF-{kappa}B activity by shifting

TNF{alpha}-induced free radical O2 to a more reduced non-radical

product H2O2 and thereby sensitizes TNF{alpha}-resistant leukemia

cells to TNF{alpha}-induced apoptosis. Importantly, wogonin does not

affect the viability of normal peripheral blood T cells. Wogonin also

sensitizes TRAIL-induced apoptosis.

Our data suggest a potential use of wogonin as a TNF{alpha} or TRAIL

adjuvant for cancer treatment. Our data also demonstrate how an herbal

compound enhances killing of tumor cells at reduced side effects

compared to other treatments.