Elucidation of mechanisms by which culinary herbs and spices exert their inhibitory action on the growth of CRC cells in vitro

Colorectal cancer (CRC) is one of the most commonly diagnosed types of cancer in the developed countries and the incidence is rising in the developing regions. Chronic inflammation, which is propagated by overexpression of cyclooxygenase-2 (COX-2) and its major product prostaglandin E2 (PGE2), plays a key role in the development of CRC. Culinary herbs and spices (CHS) are rich in polyphenols, have a high anti-oxidant capacity and possess anti-inflammatory activity. It has been shown that CHS inhibit the growth of CRC cells, however, their anti-carcinogenic mechanisms are mainly unknown. Hence, the aim of this study was to identify the CHS that were most potent inhibiting the growth of CRC cells, and subsequently to elucidate their anti-carcinogenic mechanisms, in particular, focusing on COX-2, the Wnt/β-catenin signalling pathway, and proteins involved in apoptosis. Another goal was to investigate whether combining the CHS would result in synergistic effects on the above. This study demonstrated that CHS extracted in water/or ethanol and their combinations inhibited CRC cell growth. This study also revealed that the most potent CHS extracted in ethanol (turmeric (TE), bay leaf (BLE) and ginger (GE)) and combinations downregulated the expression of COX-2 and suppressed COX-2 activity by reducing PGE2 release; their effect was comparable to that of the selective COX-2 inhibitor Celecoxib (50 μM). These CHS also induced apoptosis in CRC cells by targeting several key proteins: p53, caspase-3, and PAPR. However, the CHS did not have an effect on Wnt signalling pathway, which partially could be due to insufficient treatment time. In conclusion, this study demonstrated that CHS and their combinations inhibited CRC cell growth, inhibited COX-2 expression and activity, and modulated several key molecules involved in the development of CRC. Based on these findings, CHS have the potential to be utilized for CRC chemoprevention and possibly be used as a complimentary treatment. However, in vivo studies are needed to establish the true potential of these foods

Phytochemical investigations of three Rhodocodon (Hyacinthaceae Sensu APG II) species

The genus Rhodocodon (Hyacinthaceae sensu APG II) is endemic to Madagascar and its phytochemistry has not been described previously. The phytochemistry of three species in this genus has been investigated and eight compounds, including three bufadienolides (compounds 1, 4, and 5), a norlignan (2), and four homoisoflavonoids (compounds 3 and 6-8) have been isolated and identified. Compounds 1-3 and 6-8 have not been described previously. The COX-2 inhibitory activity of compound 6 and compound 7 acetate (compound 7A) were investigated on isolated colorectal cancer cells. Compounds 6 and 7A inhibited COX-2 by 10% and 8%, respectively, at a concentration of 12.5 M compared to 12% for 1 mM aspirin (the positive control)

Inhibitory effects of culinary herbs and spices on the growth of HCA-7 colorectal cancer cells and their COX-2 expression

It is unclear if the anti-inflammatory properties of culinary herbs and spices (CHS) are linked to their ability to inhibit Colorectal cancer cell (CRC) growth. Furthermore, their therapeutic potential with regards to CRC is unknown. The aim of this study was to establish if the inhibition of HCA-7 CRC cell growth by a selection of culinary herbs and spices (CHS) is linked to the inhibition of the cells’ cyclooxygenase-2 (COX-2 )expression, and to investigate their therapeutic potential. CHS inhibited the growth of Human colon adenocarcinoma-7 (HCA-7) cells; the order of potency was turmeric, bay leaf, ginger, sage, and rosemary; their combinations had a synergistic or additive effect on cell growth inhibition. CHS also inhibited COX-2 expression and activity; this action was comparable to that of the specific COX-2 inhibitor Celecoxib. Coincident with COX-2 inhibition was the accumulation of cells in the sub G1 phase of the HCA-7’s cell cycle and, using bay leaf and turmeric, the cleavage of caspase 3 and poly (ADP-ribose) polymerase (PARP). This latter effect showed that the effect of these CHS on growth arrest was irreversible, and was comparable to that of the caspase activator Etoposide. This study provides evidence of a link between the inhibition of HCA-7 growth, and its COX-2 expression, by CHS, and their therapeutic potential

An investigation of the effect of culinary herbs on growth of colorectal cancer cells 'in vitro'

In the UK, colorectal cancer (CRC) is one of the most commonly diagnosed cancers and studies have identified COX-2 and the Wnt/ß-catenin signalling pathway, as key to the development of CRC. Culinary herbs, and their polyphenolie constituents, have been shown to inhibit COX-2 expression and inhibit the growth of cancer cells. However, few studies have investigated their effect onCRC cells. Thus the aim of this study was to investigate whether culinary herbs inhibit the growth of human CRC cells in vitro, and to determine the role of COX-2 expression and the Wnt /[beta]-catenin signalling pathway in this action. Aqueous and ethanol extracts of the culinary herbs bay leaf, parsley, rosemary sage and thyme were tested on CRC cell lines HT29 (COX-2 positive) and HCT116 (COX-2 negative). Growth inhibition studies revealed that with the exception of aqueous extracts of parsley all the other herb extracts inhibited the growth of HCT116 and HT29 cells in vitro. The IC50s varied based on the type of extract and cell type, suggesting that polyphenol composition within the extracts and cell type influenced the potency of the herbs. Western blotting showed that some herb extracts down-regulated COX-2 and unphosphorylated [beta]-catenin expression in the HT29 cell line, however, due to the poor quality of some of the blots, a more complete establishment of this effect was not possible. In conclusion, culinary herbs inhibit the growth of CRC cells in vitro however whether such an effect occurs in vivo requires further investigation. Some culinary herb extracts down-regulated COX-2 and unphosphorylated [beta]-catenin in HT29 cells, however, future studies are needed to confirm whether culinary herbs, and their constituent polyphenols, indeed modulate these two molecular targets as part of the prevention and/or treatment of CRC

Phytochemical Investigations of Three <i>Rhodocodon</i> (Hyacinthaceae Sensu APG II) Species

The genus <i>Rhodocodon</i> (Hyacinthaceae sensu APG II) is endemic to Madagascar, and its phytochemistry has not been described previously. The phytochemistry of three species in this genus has been investigated, and eight compounds, including three bufadienolides (compounds <b>1</b>, <b>4</b>, and <b>5</b>), a norlignan (<b>2</b>), and four homoisoflavonoids (compounds <b>3</b> and <b>6</b>–<b>8</b>), have been isolated and identified. Compounds <b>1</b>–<b>3</b> and <b>6</b>–<b>8</b> have not been described previously. The COX-2 inhibitory activity of compound <b>6</b> and compound <b>7</b> acetate (compound <b>7A</b>) was investigated on isolated colorectal cancer cells. Compounds <b>6</b> and <b>7A</b> inhibited COX-2 by 10% and 8%, respectively, at a concentration of 12.5 μM compared to 12% for 1 mM aspirin (the positive control)