Wogonin sensitizes resistant malignant cells to TNFalpha- and TRAIL-induced apoptosis
Stefanie C Fas1, Sven Baumann, Jia Yun Zhu
1Tumor Immunology Program D030, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Abstract:
TNFalpha has previously been used in anticancer therapy. However, the therapeutic application of TNFalpha was largely limited due to its general toxicity and the fact that it activates the NF-kappaB-family transcription factors, which are proinflammatory and antiapoptotic. To overcome this problem in vitro, specific NF-kappaB inhibitors or transcription or protein synthesis inhibitors such as actinomycin D and cycloheximide are usually used in combination to increase TNFalpha 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-kappaB activity by shifting TNFalpha-induced free radical .O(2)(-) to a more reduced nonradical product, H(2)O(2), and thereby sensitizes TNFalpha-resistant leukemia cells to TNFalpha-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 TNFalpha 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.
Insights
Wogonin, a herbal compound, enhances tumor cell killing by sensitizing leukemia cells to TNFalpha-induced apoptosis. This natural adjuvant shows promise for cancer therapy with reduced side effects compared to conventional treatments.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Tumor Necrosis Factor alpha (TNFalpha) has shown anticancer potential but is limited by toxicity and activation of pro-inflammatory NF-kappaB pathways.
- Current in vitro methods to enhance TNFalpha efficacy involve toxic inhibitors with harmful in vivo side effects.
Purpose of the Study:
- To investigate wogonin, a compound from Huang-Qin, as a potential adjuvant to enhance TNFalpha and TRAIL-induced cancer cell apoptosis.
- To evaluate wogonin's mechanism in sensitizing TNFalpha-resistant cells and its safety profile on normal cells.
Main Methods:
- Assessed wogonin's effect on NF-kappaB activity and TNFalpha-induced apoptosis in leukemia cells.
- Investigated the role of reactive oxygen species (ROS) modulation, specifically the shift from superoxide radical (.O(2)(-)) to hydrogen peroxide (H(2)O(2)).
- Evaluated wogonin's impact on the viability of normal peripheral blood T cells and its effect on TRAIL-induced apoptosis.
Main Results:
- Wogonin attenuates NF-kappaB activity by altering TNFalpha-induced free radical (.O(2)(-)) to H(2)O(2), sensitizing resistant leukemia cells to apoptosis.
- Wogonin demonstrated selectivity, not affecting the viability of normal T cells.
- Wogonin also enhanced apoptosis induced by TRAIL (TNF-related apoptosis-inducing ligand).
Conclusions:
- Wogonin acts as a potent adjuvant, enhancing TNFalpha and TRAIL-mediated cancer cell apoptosis.
- Wogonin offers a potentially safer alternative for cancer treatment by reducing side effects associated with conventional therapies.
- This study highlights the therapeutic potential of herbal compounds in cancer treatment strategies.
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