Inhibitory Effects of Chlorogenic Acid Containing Green Coffee Bean Extract on Lipopolysaccharide-Induced Inflammatory Responses and Progression of Colon Cancer Cell Line.

An inflammatory response, related to colorectal cancer (CRC) progression, is a major subsequent result of bacterial infection following CRC surgery and should be of serious concern. Lipopolysaccharide (LPS), from the bacterial membrane, is a vital mediator of this event through binding with a Toll-like receptor 4 (TLR4) and activating through NF-κB in CRC. To identify a novel inhibitor of LPS-induced colon cancer cells (SW480), green coffee bean extract (GBE) was investigated. Ethyl acetate insoluble fraction (EIF) was mainly collected from GBE and classified as chlorogenic acid (CGA)-rich fractions. EIF and CGA inhibited TLR4 expression in LPS-induced SW480 cells. However, EIF was more dominant than CGA, via inhibition of expression and secretion of several associated mediators in inflammatory responses and CRC metastasis through NF-κB inactivation, which resulted in the abrogation of CRC migration and invasion. Thus, CGA-rich fraction from GBE can be further developed as an alternative treatment, coupled with CRC surgical treatment, to increase therapeutic efficiency and survival rate.

Gamma-Oryzanol-Rich Fraction from Purple Rice Extract Attenuates Lipopolysaccharide-Stimulated Inflammatory Responses, Migration and VEGFA Production in SW480 Cells via Modulation of TLR4 and NF-κB Pathways.

Inflammatory response facilitating colorectal cancer (CRC) progression is a serious event following operative infection, which can occur in CRC patients. This event is mainly mediated by bacterial lipopolysaccharide (LPS), via a toll like receptor 4 (TLR4) and NF-κB. Hexane soluble fraction (HSF) from purple rice extract (PRE) has been identified as a γ-oryzanol (OR)-rich fraction. Recently, HSF possessed inhibitory effect of LPS-stimulated metastasis of human colon cancer SW480 cells, however the related mechanism was unknown. Thus, this study aimed to investigate the effect of HSF on inflammatory response-associated cancer progression of LPS-stimulated SW480 cells. The various inflammatory mediators, vascular endothelial growth factor-A (VEGFA) and related pathways were evaluated by Western blot and ELISA. Furthermore, cell migration was also determined by migration assays. Of all, HSF seemed to be stronger than OR to attenuate the responsiveness of LPS on various inflammatory mediators, which was related to an obvious reduction of cancer cell migration as well as indistinct disruption on VEGFA production in SW480 cells, via downregulation of TLR4 and NF-κB. Therefore, OR-rich fraction from PRE, against the subsequent inflammatory response and CRC progression following surgery, which could be combined with conventional treatments to increase the survival rate.

Inhibitory effect of a gamma-oryzanol-rich fraction from purple rice extract on lipopolysaccharide-induced metastasis in human colon cancer cells.

The incidence of colon cancer recurrence and metastasis is known to increase as an adverse effect related to postoperative infection. Lipopolysaccharide or LPS, which is derived from gram-negative bacteria, is a key inducer of inflammatory-related tumor metastasis. Although there are numerous known biological effects of purple rice extract (PRE), its protective effect on colon metastasis was unknown. This study first evaluated the effects of hexane soluble fraction (HSF) or γ-oryzanol-rich fraction of PRE on LPS-induced colon cancer adhesion and invasion, which was accomplished using adhesive and invasive assay. Gelatin zymography was also utilized for gelatinase activity and secretion. Its chelating activity was also further analyzed by reverse gelatin zymography with zinc chloride. The study findings support the synergistic effect of HSF in protection against adverse events from LPS-induced colon cancer metastasis, as shown by effects on adhesive and invasive ability as well as matrix metalloproteinase-2 secretion and activity. PRACTICAL APPLICATIONS: Bacterial infection is still one of the main adverse events following abdominal cancer surgery and is associated with an increased incidence of colon cancer metastasis. Lipopolysaccharide (LPS) is a major component of this pathogen-mediated response. This first study investigated the efficiency of a gamma-oryzanol (OR) rich fraction, collected from purple rice extract (PRE), against LPS-induced colon cancer metastasis that occurs via three main steps; adhesion to the extracellular matrix, the secretion, and activity of gelatinase and further tissue invasion. The acquired data supported the role of an OR-rich fraction from PRE as a potential inhibitor to LPS-induced colon cancer progression. This finding, related to PRE, could be further developed to create a new adjunctive treatment to reduce operative complications related to bowel cancer surgery as well as increasing the value of this crop in Thailand.

Inhibitory effects of dried longan (Euphoria longana Lam.) seed extract on invasion and matrix metalloproteinases of colon cancer cells.

The critical step in colorectal cancer progression and associated mortality is cancer invasion, which depends on two key gelatinase enzymes, matrix metalloproteinases-2 and -9. Dried longan ( Euphoria longana Lam.) seed is a rich natural source of antioxidant polyphenols.This study evaluated the effect of dried longan seeds on colon cancer cell invasion via gelatinase function and expression. Three dried longan seed fractions were collected by Sephadex LH-20 column chromatography. They showed a potent inhibitor on colorectal cancer cell invasion and gelatinase activity. The antigelatinase activities of fractions 1 and 2 were a direct effect via Zn²âº chelation, whereas fraction 3 modulated indirectly through suppression of zymogen activators. Among the fractions, only fraction 3 reduced the gelatinase expression, which was correlated with the levels of tissue inhibitor of metalloproteinase-1 and may as well involve the p38 mitogen-activated protein kinases and the c-Jun N-terminal kinase signaling pathways. This primary research has manifested and encouraged the anticancer properties of dried longan seed extracts with potential inhibitory effects on cancer cell invasion as well as antigelatinase activity and expression in colon cancer cells.