Piper betle leaves are widely cultivated in Malaysia, India, Indonesia and Thailand. They have been used as a
traditional medicine for centuries due to their medicinal properties, including
antioxidant, antiproliferative, antibacterial, antifungal and anti-inflammatory properties, which are attributable to their high phenolic contents.
Hydroxychavicol (HC), a primary constituent of P. betle leaves, is known to possess antiproliferative activity at micromolar doses on various
cancer cell lines of different origins while leaving normal cells unharmed. The present review summarises the mechanisms of action of HC reported in the literature, reviews the scope of work done thus far and outlines the direction of future research on the potential of HC as an
anticancer agent. PubMed, Scopus and Web of Science were searched using the keywords (
hydroxychavicol OR 4-
allylpyrocatechol OR 4-allylcatechol) AND (
cancer OR
carcinogenesis OR tumour OR
carcinoma) to acquire research articles. In vitro studies reported several possible mechanisms for the chemopreventive effects of HC against
cancer cell lines, including chronic myelogenous leukaemia (CML), prostate,
glioma, breast and
colorectal cancers, while in vivo studies encompassed investigations on Ehrlich
ascites carcinoma cells in Swiss albino mice and a CML mouse model. These studies suggest that HC exerts its anticancer effect via the modulation of mitochondrial membrane potential and the
c-Jun N-terminal kinase,
mitogen-activated protein kinase and endoplasmic reticulum-unfolded protein responses pathways and the generation of
reactive oxygen species. In summary, future research should focus on combinations of HC with other anticancer drugs and testing in animal models to evaluate its bioavailability, potency and tissue and dose selectivity.