Abstract
Kava, the extract of the roots of Piper methysticum, has been traditionally consumed in the South Pacific islands for its natural relaxing
property. Epidemiological data suggests that kava consumption may reduce human cancer
risk, and in vitro and in vivo models suggest chemopreventive potential against carcinogen-induced tumorigenesis.
Therefore, knowledge about its molecular mechanisms and responsible ingredient(s)
for these beneficial properties will better guide kavaʼs use for the management of
these disorders. Psychological stress typically results in increased production of
stress hormones, such as norepinephrine (NE), which activate adrenergic receptors
(ARs). Psychological stress has also been associated with increased cancer incidence
and poor clinical outcomes in cancer patients. Mechanistically, binding of NE to ARs
induces intracellular calcium influx, which activates downstream signaling pathways
involved in both stress and cancer development. In this study, we characterized the
effect of kava and its components, 3 fractions and 6 major kavalactones, on NE-induced
intracellular calcium influx in H1299, a human non-small cell lung carcinoma cell
line. Results show that kava extract effectively inhibits NE-mediated intracellular
calcium influx in H1299 cells, potentially through antagonizing β-AR signaling. This inhibitory activity is recapitulated by the major kavalactones
in kava. Among the 6 major kavalactones, DHK demonstrated the best potency. Taken
together, our study suggests a novel mechanism through which kava and its ingredients
potentially offer the anxiolytic and cancer-preventive activity.
Key words
kava - kavalactones - stress - cancer prevention - norepinephrine - calcium -
Piper methysticum
- Piperaceae
