Wogonin sensitizes resistant malignant cells to TNFα- and TRAIL-induced apoptosis

TNF alpha has previously been used in anticancer 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 proinflammatory and antiapoptotic. To overcome this problem in vitro, specific NF-kappa B inhibitors or 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 (.) O-2(-) to a more reduced nonradical 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 a herbal compound enhances killing of tumor cells with reduced side effects compared with other treatments.