Human bitter taste-sensing type 2 receptors (hTAS2Rs) are expressed in various human tissues and may be associated with various cell signaling pathways, cell progression, and cell physiology in each tissue. hTAS2Rs can be a potential drug target because it is also expressed in some cancer cells. Xanthorrhizol (XNT) has various biological activities, such as anticancer, antimicrobial, anti-inflammatory, and antioxidant. XNT produces a bitter taste, but the specific hTAS2R activated is unknown, and the hTAS2R-mediated effect of XNT on cancer cells has not been studied. This study discovered the target receptor of XNT among 25 hTAS2Rs and confirmed the possibility of the hTAS2R-mediated inhibition of cancer cell proliferation. XNT activated only one receptor, hTAS2R38 (EC50=1.606±0.021 g/mL), and its activity was inhibited by probenecid, a hTAS2R38 antagonist. When HepG2 and MCF-7 cells were treated with XNT or phenylthiocarbamide (PTC), a known hTAS2R38 agonist, both chemicals inhibited cancer cell proliferation. XNT targets the human bitter taste receptor TAS2R38 and inhibits the proliferation of HepG2 and MCF-7 cells mediated by TAS2R38. This suggests that TAS2R38 may be a new target for disease treatment and a potential new factor for drug development.

I. Introduction
II. Materials and Methods
    1. Materials
    2. Cell culture and transfection
    3. Calcium imaging analyses
    4. Cell viability
    5. Statistical analysis
III. Results
    1. XNT activates only a single receptor hTAS2R38
    2. PTC and XNT are inactivated by TAS2R38 antagonist
    3. XNT regulates cell proliferation in HepG2 and MCF-7cell lines via hTAS2R38
IV. Discussion
V. Summary and Conclusion
Acknowledgment
Conflict of Interest
References

• Yiseul Kim(Korea Food Research Institute)
• Hyun-Jin Na(Korea Food Research Institute)
• Min Jung Kim(Korea Food Research Institute) Corresponding author