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Published on: June 12, 2021
Anticancer agent xanthohumol inhibits IL-2 induced signaling pathways involved in T cell proliferation
Yongbo Liu1, Xiaohua Gao, Dorrah Deeb
1Department of Surgery, Henry Ford Health System, Detroit, MI 48202, USA.
Abstract:
Xanthohumol (XN), a prenylated chalcone present in hops exhibits anti-inflammatory, antioxidant and anticancer activity. In the present study we show that XN inhibits the proliferation of mouse lymphoma cells and IL-2 induced proliferation and cell cycle progression in mouse splenic T cells. The suppression of T cell proliferation by XN was due to the inhibition of IL-2 induced Janus kinase/signal transducers and activators of transcription (Jak/STAT) and extracellular signal-regulated kinase 1 and 2 (Erk1/2) signaling pathways. XN also inhibited proliferation-related cellular proteins such as c-Myc, c-Fos and NF-kappaB and cyclin D1. Thus, understanding of IL-2 induced cell signaling pathways in normal T cells, which are constitutively turned on in T cell lymphomas may facilitate development of XN for the treatment of hematologic cancers.
Insights
Xanthohumol (XN), found in hops, inhibits lymphoma and T cell proliferation by blocking key signaling pathways. This suggests XN
Area of Science:
- Biochemistry
- Immunology
- Pharmacology
Background:
- Xanthohumol (XN), a prenylated chalcone from hops, possesses known anti-inflammatory, antioxidant, and anticancer properties.
- T cell proliferation is crucial in immune responses and can be dysregulated in hematologic cancers.
Purpose of the Study:
- To investigate the effects of Xanthohumol (XN) on mouse lymphoma and T cell proliferation.
- To elucidate the molecular mechanisms underlying XN's antiproliferative effects on T cells.
Main Methods:
- Treatment of mouse lymphoma cells and normal mouse splenic T cells with XN.
- Analysis of cell proliferation, cell cycle progression, and key signaling pathways (Jak/STAT, Erk1/2).
- Western blot analysis to assess protein expression (c-Myc, c-Fos, NF-kappaB, cyclin D1).
Main Results:
- XN significantly inhibited the proliferation of mouse lymphoma cells.
- XN suppressed Interleukin-2 (IL-2) induced proliferation and cell cycle progression in mouse splenic T cells.
- XN blocked IL-2 induced Jak/STAT and Erk1/2 signaling pathways and reduced levels of proliferation-related proteins.
Conclusions:
- XN exhibits antiproliferative effects on both lymphoma and normal T cells.
- The mechanism involves the inhibition of critical IL-2 signaling pathways and proliferation-associated proteins.
- XN shows potential as a therapeutic agent for hematologic cancers by targeting these pathways.
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