Hydroxychavicol as a potential anticancer agent (Review).

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.

Tumor Suppressive Effects of GAS5 in Cancer Cells.

In recent years, long non-coding RNAs (lncRNAs) have been shown to play important regulatory roles in cellular processes. Growth arrests specific transcript 5 (GAS5) is a lncRNA that is highly expressed during the cell cycle arrest phase but is downregulated in actively growing cells. Growth arrests specific transcript 5 was discovered to be downregulated in several cancers, primarily solid tumors, and it is known as a tumor suppressor gene that regulates cell proliferation, invasion, migration, and apoptosis via multiple molecular mechanisms. Furthermore, GAS5 polymorphism was found to affect GAS5 expression and functionality in a cell-specific manner. This review article focuses on GAS5's tumor-suppressive effects in regulating oncogenic signaling pathways, cell cycle, apoptosis, tumor-associated genes, and treatment-resistant cells. We also discussed genetic polymorphisms of GAS5 and their association with cancer susceptibility.

Bisphenol A and its effects on the systemic organs of children.

For the past two decades, growing research has been pointing to multiple repercussions of bisphenol A (BPA) exposure to human health. BPA is a synthetic oestrogen which primarily targets the endocrine system; however, the compound also disturbs other systemic organ functions, in which the magnitude of impacts in those other systems is as comparable to those in the endocrine system. To date, the discoveries on the association between BPA and health outcomes mainly came from animal and in vitro studies, with limited human studies which emphasised on children's health. In this comprehensive review, we summarised studies on human, in vivo and in vitro models to understand the consequences of pre-, post- and perinatal BPA exposure on the perinatal, children and adult health, encompassing cardiovascular, neurodevelopmental, endocrine and reproductive effects.Conclusion: Evidence from in vitro and animal studies may provide further support and better understanding on the correlation between environmental BPA exposure and its detrimental effects in humans and child development, despite the difficulties to draw direct causal relations of BPA effects on the pathophysiology of the diseases/syndromes in children, due to differences in body system complexity between children and adults, as well as between animal and in vitro models and humans. What is known: • Very limited reviews are available on how BPA adversely affects children's health. • Previous papers mainly covered two systems in children. What is new: • Comprehensive review on the detrimental effects of BPA on children health outcomes, including expectations on adult health outcomes following perinatal BPA exposure, as well as covering a small part of BPA alternatives. • Essentially, BPA exposure during pregnancy has huge impacts on the foetus in which it may cause changes in foetal epigenetic programming, resulting in disease onsets during childhood as well as adulthood.

Tocotrienol-rich fraction, [6]-gingerol and epigallocatechin gallate inhibit proliferation and induce apoptosis of glioma cancer cells.

Plant bioactives [6]-gingerol (GING), epigallocatechin gallate (EGCG) and asiaticoside (AS) and vitamin E, such as tocotrienol-rich fraction (TRF), have been reported to possess anticancer activity. In this study, we investigated the apoptotic properties of these bioactive compounds alone or in combination on glioma cancer cells. TRF, GING, EGCG and AS were tested for cytotoxicity on glioma cell lines 1321N1 (Grade II), SW1783 (Grade III) and LN18 (Grade IV) in culture by the (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. With the exception of AS, combinations of two compounds were tested, and the interactions of each combination were evaluated by the combination index (CI) using an isobologram. Different grades of glioma cancer cells showed different cytotoxic responses to the compounds, where in 1321N1 and LN18 cells, the combination of EGCG + GING exhibited a synergistic effect with CI = 0.77 and CI = 0.55, respectively. In contrast, all combinations tested (TRF + GING, TRF + EGCG and EGCG + GING) were found to be antagonistic on SW1783 with CI values of 1.29, 1.39 and 1.39, respectively. Combined EGCG + GING induced apoptosis in both 1321N1 and LN18 cells, as evidenced by Annexin-V FITC/PI staining and increased active caspase-3. Our current data suggests that the combination of EGCG + GING synergistically induced apoptosis and inhibits the proliferation 1321N1 and LN18 cells, but not SW1783 cells, which may be due to their different genetic profiles.