**Background**
Cancer and viral infections remain significant global health challenges, necessitating the discovery of multi-target therapeutic agents. In particular, the inhibition of angiogenesis and the induction of apoptosis are critical strategies for suppressing tumor growth and metastasis. Furthermore, the management of chronic inflammation and viral replication requires compounds that can modulate key signaling pathways and enzymatic activities. Flavonoids, naturally occurring polyphenolic compounds, have gained attention for their diverse pharmacological properties, including anti-inflammatory and antitumor activities. In this context, we will introduce a potent flavonoid isolated from hops – Xanthohumol.
**Definition**
Xanthohumol is a principal flavonoid that acts as an inhibitor of diacylglycerol acetyltransferase (DGAT), COX-1, and COX-2. According to the Xanthohumol description, it exhibits significant anti-cancer, anti-angiogenic, and antiviral activities.
**In Vitro Studies**
The Xanthohumol biological activity has been extensively documented across various cell lines and physiological systems. In terms of cardiovascular and hematological effects, Xanthohumol significantly attenuates ADP-induced blood platelet aggregation and reduces the expression of the activated fibrinogen receptor (GPIIbIIIa) on platelet surfaces. In rat ventricular myocytes, concentrations of 5-50 nM reduce the frequency of spontaneously occurring Ca2+ sparks and waves, while 50-100 nM reduces the rate of relaxation of Ca2+ transients and suppresses SR Ca2+ content.
Regarding Xanthohumol Cancer research, the compound demonstrates potent cytotoxicity and antiproliferative effects. In glioma cells, it induces apoptosis via pro-caspase-3/8 cleavage, PARP degradation, and mitochondrial dysfunction, specifically inhibiting the IGFBP2/AKT/Bcl2 pathway through miR-204-3p targeting. In endothelial cells, it activates AMPK via CAMMKβ (but not LKB1), which subsequently reduces nitric oxide (NO) levels by decreasing eNOS phosphorylation, thereby mediating its anti-angiogenic activity. Additionally, the AKT pathway is inactivated independently of AMPK.
Xanthohumol in vitro data shows varying IC50 values across multiple human cell lines: it exhibits cytotoxicity against Ishikawa cells (IC50 = 4.2 μM), BGC-823 cells (IC50 = 7.8 μM), and MCF7 cells (IC50 = 3.47 μM after 4 days). It also shows antiproliferative activity against A549 cells (IC50 = 11.9 μM), HeLa cells (IC50 = 9.4 μM), and NCI-H460 cells (IC50 = 6.9 μM). Furthermore, it demonstrates antiviral activity against bovine viral diarrhea virus (BVDV), rhinovirus, HSV-1, HSV-2, and cytomegalovirus (CMV). In conclusion, Xanthohumol is a multi-functional flavonoid with broad applications in oncology, virology, and cardiovascular research.
Keywords
Xanthohumol, 6754-58-1, COX, Acyltransferase, Apoptosis, HSV, CMV, Influenza Virus, Cyclooxygenase, Diacylglycerol acyltransferase, Diglyceride acyltransferase, acyl-CoA:cholesterol acyltransferase, mono- acylglycerol acyltransferase, Herpes simplex virus, Cytomegalovirus
References
[1] Luzak B, et al. Xanthohumol from hop cones (Humulus lupulus L.) prevents ADP-induced platelet reactivity. Arch Physiol Biochem. 2016 Nov 18:1-7
[2] Arnaiz-Cot JJ, et al. Xanthohumol modulates calcium signaling in rat ventricular myocytes: Possible Antiarrhythmic properties. J Pharmacol Exp Ther. 2016 Nov 4. pii: jpet.116.236588
[3] Gallo C, et al. Hop derived flavonoid xanthohumol inhibits endothelial cell functions via AMPK activation. Oncotarget. 2016 Aug 1
[4] Chen PH, et al. The miR-204-3p-targeted IGFBP2 pathway is involved in xanthohumol-induced glioma cell apoptotic death. Neuropharmacology. 2016 Nov;110(Pt A):362-75.
[5] Buckwold VE, et al. Antiviral activity of hop constituents against a series of DNA and RNA viruses. Antiviral Res. 2004 Jan;61(1):57-62.
[6] Inokoshi J, et al. Expression of two human acyl-CoA:diacylglycerol acyltransferase isozymes in yeast and selectivity of microbial inhibitors toward the isozymes. J Antibiot (Tokyo). 2009;62(1):51-54.