Hydroxychavicol as a potential anticancer agent (Review)

Abstract

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. Contents 1. Introduction 2. Methods 3. Composition of HC 4. In vitro and in vivo studies 5. Anti-inflammatory activity of HC 6. Conclusions and prospects

Identifying the Structural Components Responsible for the Antiproliferative Properties of Hydroxychavicol

“…The structure of hydroxychavicol contains catechol, which is known to have antiproliferative properties [3,4,[6][7][8]13,27,28]. Our study demonstrates that the presence of the catechol-like structure is key for the antiproliferative activity of hydroxychavicol and that the attachment of an aliphatic chain to the catechol structure dampens that activity (Figure 3).…”

“…Its usage encompasses cultural, spiritual, and medical matters. Research has shown that this herb has antioxidative, anti-inflammatory, antibacterial, and anticancer properties [1][2][3][4][5][6][7].…”

“…Other studies have shown that eugenol and hydroxychavicol have anticarcinogenic properties as well. Both compounds appear to be exerting their antiproliferative effect through the PI3K/AKT/mTOR pathway in multiple cancer cell lines, including colon, breast, lung, and melanoma, by causing the downregulation of cell cycle-related transcription factors [16], the inhibition of oncogenes [17], and inducing apoptosis and autophagy [6,[18][19][20][21][22][23][24][25][26].…”

Molecular Docking Analysis of Hydroxyclavicol and Eugenol From Betel Leaves Against Outer Membrane Protein (OmpH) of Dialister pneumosintes

“…The deep heart-shaped leaves of Piper betle, also known as betel leaves, are a natural source of hydroxychavicol (4-allyl-cat-epil, 1-allyl-3,4dihydroxybenzene), a significant phenolic component that has historically been utilized as a mouth freshener in eastern Asian native countries. It has been shown to possess the ability to trigger apoptosis in cells via the induction of oxidative stress, depletion of glutathione (GSH), and modulation of the cell cycle [11]. By stimulating the body's innate immunological response, hydroxychavicol also has anticancer effects.…”

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“…Hydroxychavicol, a phenyl propanoid compound isolated from the chloroform extraction of an aqueous extract of Piper betel leaves, showed inhibitory activity against oral cavity pathogens. Hydroxychavicol (HC), is known to possess antiproliferative activity at micromolar doses on various cancer cell lines of different origins while leaving normal cells unharmed 1 . It exhibited an inhibitory effect on all of the oral cavity pathogens tested (MICs of 62.5 to 500 g/ml) with a minimal bactericidal concentration that was two-fold greater than the inhibitory concentration 2 .…”