Dietary citrulline does not modify rat colon tumor response to chemotherapy, but failed to improve nutritional status.

During cancer therapy many patients experience significant malnutrition, leading to decreased tolerance to chemotherapy and decreased survival. Dietary citrulline supplementation improves nutritional status in situations such as short bowel syndrome and aging, and is of potential interest in oncology. However, a mandatory prerequisite is to test this amino acid for interaction with tumor growth and chemotherapy response. Dietary citrulline (Cit; 2%), or an isonitrogenous mix of non-essential amino acids (control), was given to Ward colon tumor-bearing rats the day before chemotherapy initiation. Chemotherapy included 2 cycles, one week apart, each consisting of one injection of CPT-11 (50 mg/kg) and of 5-fluorouracil (50 mg/kg) the day after. Body weight, food intake and tumor volume were measured daily. The day after the last injection, rats were killed, muscles (EDL, gastrocnemius), intestinal mucosa, tumor, spleen and liver were weighed. Muscle and intestinal mucosa protein content were measured. Phosphorylated 4E-BP1 was measured in muscle and tumor as a surrogate for biosynthetic activation. FRAPS (Ferric Reducing Ability of Plasma) and thiols in plasma, muscle and tumor were evaluated and plasma amino acids and haptoglobin were measured. Numerous parameters did not differ by diet overall: a) response of tumor mass to treatment, b) tumor antioxidants and phosphorylated 4E-BP1 levels, c) relative body weight and relative food intake, d) weight of EDL, gastrocnemius, intestinal mucosa, spleen and liver and e) plasma haptoglobin concentrations. Moreover, plasma citrulline concentration was not correlated to relative body weight, only cumulated food intake and plasma haptoglobin concentrations were correlated to relative body weight. Citrulline does not alter the tumor response to CPT-11/5FU based therapy but, has no effect on nutritional status, which could be due to the anorexia and the low amount of citrulline and protein ingested.

Effect of herbal medicine daikenchuto on gastrointestinal symptoms following laparoscopic colectomy in patients with colon cancer: A prospective randomized study.

We conducted a prospective randomized study to investigate the effect of daikenchuto (DKT) on abdominal symptoms following laparoscopic colectomy in patients with left-sided colon cancer. Patients who suffered from abdominal pain or distention on postoperative day 1 were randomized to either the DKT group or non-DKT group. The primary endpoints were the evaluation of abdominal pain, abdominal distention, and quality of life. The metabolome and gut microbiome analyses were conducted as secondary endpoints. A total of 17 patients were enrolled: 8 patients in the DKT group and 9 patients in the non-DKT group. There were no significant differences in the primary endpoints and postoperative adverse events between the two groups. The metabolome and gut microbiome analyses showed that the levels of plasma lipid mediators associated with the arachidonic acid cascade were lower in the DKT group than in the non-DKT group, and that the relative abundance of genera Serratia and Bilophila were lower in the DKT group than in the non-DKT group. DKT administration did not improve the abdominal symptoms following laparoscopic colectomy. The effects of DKT on metabolites and gut microbiome have to be further investigated.

Impact of phytochemicals and plant extracts on viability and proliferation of NK cell line NK-92 - a closer look at immunomodulatory properties of goji berries extract in human colon cancer cells.

INTRODUCTION: Due to the fact that lymphocytes NK (natural killer cells) are the first line of defence of the body against cancer, one of the goals of modern immunotherapy is the enhancement of their natural activities for the effective recognition, detection, and elimination of cancer cells. OBJECTIVE: The aim of the study was to evaluate the influence of selected phytochemicals (curcumin and resveratrol) and plant extracts (chlorella and goji berries) on NK cells viability and proliferation, as well as cytotoxic activity against colon cancer - one of the most common cancer worldwide. MATERIAL AND METHODS: The impact of phytochemicals, viability and proliferation of plant extracts on NK cells was examined in NK-92 cells using both LDH and MTT assays. The immunomodulatory properties of selected compounds were tested against human colon cancer cell line LS180 using the MTT test. RESULTS: Extracts of chlorella and goji berries significantly increased NK cell proliferation, while curcumin and resveratrol did not affect this process. Curcumin, as well as extracts of chlorella and goji berries, did not impact NK viability, while resveratrol significantly increased it. LDH test revealed the cytotoxic effect of chlorella extract and curcumin in NK-92 cell cultures. On the contrary, goji berries extract significantly decreased LDH level, while resveratrol did not affect the integrity of NK cell membranes. Studies conducted in co-cultures NK cells, also directly eliminated colon cancer cells. CONCLUSIONS: Performed studies revealed immunomodulatory properties of goji berries extract, which improved viability and proliferation of NK cells, and above all, significantly increased their ability to recognize and eliminate colon cancer cells.

Lysosome-Mediated Cytotoxic Autophagy Contributes to Tea Polysaccharide-Induced Colon Cancer Cell Death via mTOR-TFEB Signaling.

Targeting autophagy and lysosome may serve as a promising strategy for cancer therapy. Tea polysaccharide (TP) has shown promising antitumor effects. However, its mechanism remains elusive. Here, TP was found to have a significant inhibitory effect on the proliferation of colon cancer line HCT116 cells. RNA-seq analysis showed that TP upregulated autophagy and lysosome signal pathways, which was further confirmed through experiments. Immunofluorescence experiments indicated that TP activated transcription factor EB (TFEB), a key nuclear transcription factor modulating autophagy and lysosome biogenesis. In addition, TP inhibited the activity of mTOR, while it increased the expression of Lamp1. Furthermore, TP ameliorated the lysosomal damage and autophagy flux barrier caused by Baf A1 (lysosome inhibitor). Hence, our data suggested that TP repressed the proliferation of HCT116 cells by targeting lysosome to induce cytotoxic autophagy, which might be achieved through mTOR-TFEB signaling. In summary, TP may be used as a potential drug to overcome colon cancer.

Identification of polyphenol from Ziziphi spinosae semen against human colon cancer cells and colitis-associated colorectal cancer in mice.

Homology of medicine and food-zizyphi spinosi semen (ZSS) exhibits abundant pharmacological activities, such as sedation, hypnosis and anti-depression. In the present study, the water soluble polyphenols extracted from ZSS via the acid digestion method were named ZSSP, and exhibited significant anti-colorectal cancer (CRC) activity, characterized by restraining cell proliferation, promoting cell apoptosis and increasing chemo-sensitivity of CRC cells. The potential of ZSSP in vivo was further evaluated in an AOM/DSS-induced colitis-associated carcinogenesis (CAC) mouse model. Intriguingly, ZSSP diminished the number and volume of CAC polyps in mice in a dose-dependent manner, and effectively limited the damage of mice organs induced by AOM/DSS. The immunohistochemistry result showed that the elevated CRC early markers in CAC mice, such as COX-II, EMR1, and Ki67, were potently prevented by the ZSSP treatment. Further, the component in ZSSP with the anti-CRC activity was identified as spinosin by the macroporous resin of SP207 and RP-HPLC-MS/MS. Interestingly, during the extraction process, sodium ions were introduced forming spinosin·Na+, which had better water solubility and more remarkable anti-CRC activity than the spinosin. This study provides a new pharmacological property of spinosin derived from ZSS, inhibiting the growth of human CRC cells and colitis-associated CRC in mice, which indicates its potential use as a natural agent against CRC.

In vitro and in vivo antitumor activity of Yerba Mate extract in colon cancer models.

Yerba Mate (Ilex paraguariensis St. Hill. Aquifoliaceae) is a native South American tree and has a large amount of bioactive compounds. Colorectal cancer (CRC) is one of the so-called westernized diseases and is the third most common cancer in both men and women. Efficient strategies for the treatment of CRC are extensively being explored including dietary intervention. The objective of our research was to evaluate the effects of Yerba Mate extract on cell proliferation, invasive capacity of tumor cells, and angiogenesis. For this, in vitro and in vivo experimentation was carried out using CRC models. The extract was generated by aqueous extraction and prepared according to traditional American procedure of preparing mate infusion. In vitro results showed that the Yerba Mate extract inhibits CT26 and COLO 205 cell proliferation with IC50 values of 0.25 and 0.46 mg/mL, respectively. We demonstrated by TUNEL assay that one of the mechanisms by which Yerba Mate extract decreases cell proliferation is by induction of apoptosis. In a murine syngeneic tumor model, oral administration of Yerba Mate extract in a dose of 1.6 g/kg/day significantly inhibited angiogenesis and tumor growth without affecting biological parameters or body weight. Our findings suggest that Yerba Mate may be a promising agent for the treatment of colon cancer and could be used as an herbal medicine or functional food ingredient. PRACTICAL APPLICATION: Considering the chemical composition and presence of phenolic compounds with their free-radical scavenging activities and bioactivities against colon cancer cells, Yerba Mate can be a promising candidate as healthy food sources in human nutrition, and also be considered a natural source of potential antitumor agents. Taking into account the economic importance of Yerba Mate in Argentina, this vegetable would have a greater commercial value as a functional food.

Z-ajoene from Crushed Garlic Alleviates Cancer-Induced Skeletal Muscle Atrophy.

Skeletal muscle atrophy is one of the major symptoms of cancer cachexia. Garlic (Allium sativum), one of the world's most commonly used and versatile herbs, has been employed for the prevention and treatment of diverse diseases for centuries. In the present study, we found that ajoene, a sulfur compound found in crushed garlic, exhibits protective effects against muscle atrophy. Using CT26 tumor-bearing BALB/c mice, we demonstrate in vivo that ajoene extract alleviated muscle degradation by decreasing not only myokines secretion but also janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) and SMADs/forkhead box (FoxO) signaling pathways, thereby suppressing muscle-specific E3 ligases. In mouse skeletal myoblasts, Z-ajoene enhanced myogenesis as evidenced by increased expression of myogenic markers via p38 mitogen-activated protein kinase (MAPK) activation. In mature myotubes, Z-ajoene protected against muscle protein degradation induced by conditioned media from CT26 colon carcinoma cells, by suppressing expression of muscle specific E3 ligases and nuclear transcription factor kappa B (NF-κB) phosphorylation which contribute to muscle atrophy. Moreover, Z-ajoene treatment improved myofiber formation via stimulation of muscle protein synthesis. These findings suggest that ajoene extract and Z-ajoene can attenuate skeletal muscle atrophy induced by cancer cachexia through suppressing inflammatory responses and the muscle wasting as well as by promoting muscle protein synthesis.

Non-extractable polyphenols from cranberries: potential anti-inflammation and anti-colon-cancer agents.

Cranberries (Vaccinium macrocarpon) are full of polyphenols, which display various health benefits. Most studies have focused on extractable polyphenols (EPs) rather than non-extractable polyphenols (NEPs) but NEPs may possess important biological functions. The objective of this work was to characterize EP and NEP fractions from whole cranberries and determine their potential as anti-inflammation and anti-colon-cancer agents. Our results showed that of the identified polyphenols, anthocyanins were the major ones in the cranberry EP fraction, while phenolic acids were most abundant in the NEP fraction. The oxygen radical absorbance capacity (ORAC) of the NEPs was significantly higher than that of the EPs. Both the EPs and NEPs showed anti-inflammatory effects in inhibiting LPS-induced production of nitric oxide in macrophages. At the concentrations tested, the NEPs showed significantly higher inhibition of the production of nitric oxide in macrophages than the EPs, which was accompanied by decreased expression of inducible nitric oxide synthase (iNOS) and increased expression of HO-1. EP and NEP samples showed anti-cancer capacities in HCT116 cells. And the NEPs showed stronger inhibitory effects on the viability and colony formation capacity of human colon cancer HCT116 cells than the EPs. In a flow cytometry analysis, the NEPs caused cell cycle arrest at the G0/G1 phase and induced significant cellular apoptosis in colon cancer cells. Overall, our results suggested that both the EP and NEP fractions from cranberries were bioactive, and importantly, the NEP fraction showed promising anti-inflammation and anti-colon-cancer potential.

Ethanol extract of Chrysanthemum zawadskii Herbich induces autophagy and apoptosis in mouse colon cancer cells through the regulation of reactive oxygen species.

BACKGROUND: Recent research has suggested that autophagy can provide a better mechanism for inducing cell death than current therapeutic strategies. This study investigated the effects of using an ethanol extract of Chrysanthemum zawadskii Herbich (ECZ) to induce apoptosis and autophagy associated with reliable signal pathways in mouse colon cancer CT-26 cells. METHODS: Using ECZ on mouse colon cancer CT-26 cells, cell viability, annexin V/propidium iodide staining, acridine orange staining, reactive oxygen species (ROS) and western blotting were assayed. RESULTS: ECZ exhibited cytotoxicity in CT-26 cells in a dose-dependent manner. ECZ induced apoptosis was confirmed by caspase-3 activation, poly (ADP-ribose) polymerase cleavage, and increased production of reactive oxygen species (ROS). Furthermore, it was shown that ECZ induced autophagy via the increased conversion of microtubule-associated protein 1 light chain 3II, the degradation of p62, and the formation of acidic vesicular organelles. The inhibition of ROS production by N-Acetyl-L-cysteine resulted in reduced ECZ-induced apoptosis and autophagy. Furthermore, the inhibition of autophagy by 3-methyladenine resulted in enhanced ECZ-induced apoptosis via increased ROS generation. CONCLUSION: These findings confirmed that ECZ induced ROS-mediated autophagy and apoptosis in colon cancer cells. Therefore, ECZ may serve as a novel potential chemotherapeutic candidate for colon cancer.

Glycation affects differently the main soybean Bowman-Birk isoinhibitors, IBB1 and IBBD2, altering their antiproliferative properties against HT29 colon cancer cells.

Naturally-occurring serine protease inhibitors of the Bowman-Birk family, particularly abundant in legume seeds, exert their potential chemopreventive and/or therapeutic properties via protease inhibition. Processing of legume seeds, including soybeans, has been proposed as a major cause for their loss of bioactivity due to glycation. In order to assess how glycation affected the protease inhibitory activities of major soybean Bowman-Birk isoinhibitors (BBI) and their antiproliferative properties, IBB1 and IBBD2 were purified and subjected to glycation under controlled conditions using glucose at high temperature. Both soybean isoinhibitors showed remarkable heat stability. In the presence of glucose, IBBD2 lost most of its trypsin inhibitory activity while IBB1 maintains similar trypsin and chymotrypsin inhibitory activities as in the absence of sugar. Glycation patterns of both BBI proteins were assessed by MALDI-TOF spectrometry. Our results show that the glycation process affects IBBD2, losing partially its antiproliferative activity against HT29 colon cancer cells, while glycated-IBB1 was unaffected.

Branched mannans from the mushroom Cantharellus cibarius enhance the anticancer activity of natural killer cells against human cancers of lung and colon.

Several studies have shown that mushroom polysaccharides enhance the ability of natural killer (NK) cells to recognize cancer cells as foreign and thereby enhance the effectiveness of host immune defence mechanisms. Nevertheless, the use of NK cells in cancer treatment requires finding selective stimulators of their cytotoxicity without disturbing organism homeostasis. Our studies revealed that Cantharellus cibarius polysaccharides present in the CC2a fraction, mainly composed of an O-2 and O-3 branched (1→6)-linked mannan, not only beneficially influenced the viability and proliferation of the human natural killer cells NK92 but also enhanced their anticancer properties against the human lung and colon cancer cells A549 and LS180, and at the same time did not affect the human lung and colon epithelial cells NL20 and CCD841 CoN. Furthermore, the CC2a fraction used alone was also nontoxic to the normal epithelium, while it inhibited the viability of these cancer cells. Nevertheless, the therapeutic potential of NK92 cells was greatly enhanced after coincubation with these polysaccharides and the observed effect was dependent on the CC2a concentrations. The beneficial effect of CC2a on NK92 cells was associated with stimulation of p38 and Erk expression as well as induction of the transcription factor CREB. The discovered beneficial impact of the CC2a fraction on NK92 cells suggested the therapeutic use of the investigated compound especially as an adjuvant. Furthermore, taking into account the abundance of these water soluble mannans in C. cibarius, the results also suggest that an increase in the intake of C. cibarius may promote innate immunity response against cancer through the enhancement of NK cell activity.

Study of the antitumor mechanisms of apiole derivatives (AP-02) from Petroselinum crispum through induction of G0/G1 phase cell cycle arrest in human COLO 205 cancer cells.

BACKGROUND: Apiole was isolated from the leaves of various plants and vegetables and has been demonstrated to inhibit human colon cancer cell (COLO 205 cells) growth through induction of G0/G1 cell cycle arrest and apoptotic cell death. This study further explored the antitumor effects of apiole derivatives AP-02, 04, and 05 in COLO 205 cancer cells. METHODS: Human breast (MDA-MB-231, ZR75), lung (A549, PE089), colon (COLO 205, HT 29), and hepatocellular (Hep G2, Hep 3B) cancer cells were treated with apiole and its derivatives in a dose-dependent manner. Flow cytometry analysis was subsequently performed to determine the mechanism of AP-02-induced G0/G1 cell cycle arrest. The in vivo antitumor effect of AP-02 (1 and 5 mg/kg, administered twice per week) was examined by treating athymic nude mice bearing COLO 205 tumor xenografts. The molecular mechanisms of AP-02-induced antitumor effects were determined using western blot analysis. RESULTS: AP-02 was the most effective compound, especially for inhibition of COLO 205 colon cancer cell growth. The cytotoxicity of AP-02 in normal colon epithelial (FHC) cells was significantly lower than that in other normal cells derived from the breast, lung or liver. Flow cytometry analysis indicated that AP-02-induced G0/G1 cell cycle arrest in COLO 205 cells but not in HT 29 cells (< 5 µM for 24 h, **p < 0.01). Tumor growth volume was also significantly inhibited in AP-02 (> 1 mg/kg)-treated athymic nude mice bearing COLO 205 tumor xenografts compared to control mice (*p < 0.05). Furthermore, G0/G1 phase regulatory proteins (p53 and p21/Cip1) and an invasion suppressor protein (E-cadherin) were significantly upregulated, while cyclin D1 was significantly downregulated, in AP-02-treated tumor tissues compared to the control group (> 1 mg/kg, *p < 0.05). CONCLUSIONS: Our results provide in vitro and in vivo molecular evidence of AP-02-induced anti-proliferative effects on colon cancer, indicating that this compound might have potential clinical applications.

Brosimone I, an isoprenoid-substituted flavonoid, induces cell cycle G1 phase arrest and apoptosis through ROS-dependent endoplasmic reticulum stress in HCT116 human colon cancer cells.

Brosimone I is an isoprenoid-substituted flavonoid from Artocarpus heterophyllus. Here, we reported for the first time that brosimone I induced cell cycle G1 phase arrest and apoptosis in HCT116 human colon cancer cells. Brosimone I treatment increased the cytosolic Ca2+ level, and subsequently activated the CaMKKß-AMPK pathway. STO-609, a CaMKKß inhibitor, and compound C, an AMPK-specific inhibitor, attenuated brosimone I-induced loss of cell viability in HCT116 cells. Furthermore, brosimone I enhanced ER stress. Salubrinal, an ER stress inhibitor, reduced brosimone I-induced cell growth inhibition. In addition, brosimone I was found to increase ROS generation and the inhibition of ROS formation by NAC, a ROS inhibitor, attenuated brosimone I-induced cell death, cytosolic Ca2+ increase, and ER stress markers. Collectively, our findings reveal that brosimone I induces cell cycle G1 phase arrest and apoptosis via the induction of ROS-mediated increased cytosolic Ca2+, ER stress, and the activation of the CaMKKß-AMPK signaling pathway.

Chemopreventive Potential of Apple Pulp Callus Against Colorectal Cancer Cell Proliferation and Tumorigenesis.

This study focused on the evaluation of the chemopreventive potential of tissue in vitro culture of the "Mela Rosa Marchigiana" apple (MRM callus) that allows the amplification of secondary metabolites. The MRM pulp and MRM callus chemopreventive potential was evaluated in terms of antiproliferative activity, inhibition of tumorigenesis in soft agar cultures, cell cycle and western blotting analyses in CaCo2 and LoVo colon cancer cell lines and in JB6 promotion-sensitive (JB6 P+) cells. MRM callus induced a strong concentration-dependent inhibition of colon cancer cell proliferation and suppressed 12-o-tetra-decanoyl-phorbol-13-acetate-induced tumorigenesis of JB6 P+ cells in soft agar cultures. MRM callus inhibited the phosphorylation of JNK, p38, and eIF2alpha. Our data indicate that the MRM callus exerts a good antiproliferative and antitumorigenic potential through the MAP kinase inhibition and could provide natural compounds with chemopreventive properties.

Glyceollins Modulate Tumor Development and Growth in a Mouse Xenograft Model of Human Colon Cancer in a p53-Dependent Manner.

Glyceollins are soybean-derived phytoalexins that induce the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway, which is involved in the detoxification of carcinogens and the removal of reactive oxygen species (ROS). Recent studies, however, have indicated that Nrf2 induction stimulates the development of pre-existing tumors and confers resistance to chemotherapy by elevating drug metabolism and by efficient scavenging of ROS produced by the Warburg effect, which is regulated, in turn, by the p53 tumor suppressor. This study, therefore, aimed at examining whether glyceollins could accelerate tumor growth in the presence of active p53, using a xenograft BALB/c nude mouse model transplanted subcutaneously with p53 wild-type and p53 null HCT116 human colon cancer cells. Glyceollins were orally administered at a dose of either 1 or 4 mg/kg body weight after xenografting HCT116 cells, and tumor growth and volume were monitored for 2 weeks. A high dose of glyceollins resulted in a significant increase in the average volume of p53 wild-type HCT116 xenografts, but not of p53 null HCT116 xenografts. However, a low dose of glyceollins had no effect on the tumor growth regardless of p53 presence. Interestingly, antioxidant enzymes, including heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase, were prominently induced by glyceollins in p53 wild-type xenografts, compared with p53 null xenografts. These results suggest that a high dose of glyceollins possibly promotes the growth of p53 wild-type colon cancer through activation of the Nrf2-mediated signaling pathway and, in particular, strong induction of HO-1 expression. Therefore, the consumption of Nrf2 activators, including glyceollins, should be carefully monitored for patients suffering from certain types of cancer and/or receiving chemotherapy.

Resultados de la cirugía resectiva de pacientes con Cáncer de Colon no complicado en un centro privado y regional de salud / Results of resective surgery in patients with non-complicated Colon Cancer in a private and regional health establishment

El tratamiento estándar del cáncer de colon (CC), continúa siendo la resección radical del segmento intestinal comprometido con márgenes libres (al menos 5 cm por encima y debajo del tumor), pudiendo o no asociarse a terapias complementarias. El objetivo de este estudio fue determinar morbilidad postoperatoria (MPO) y supervivencia actuarial global (SVAG) a 5 años en pacientes resecados por CC no complicado. La metodología usada fue serie de casos retrospectiva de pacientes con CC no complicado, sometidos a colectomía subtotal y linfadenectomía, de forma consecutiva, en Clínica RedSalud Mayor Temuco, entre 2007 y 2017. La variable resultado fue SV actuarial global (SVAG) a 5 años. Otras variables de interés fueron: tiempo quirúrgico, número de linfonodos resecados, estancia hospitalaria, MPO, y recurrencia. Los pacientes fueron seguidos de forma clínica. Se utilizó estadística descriptiva, con medidas de tendencia central y dispersión; y análisis de SV con curvas de Kaplan Meier. Se intervinieron 43 pacientes (58,1 % hombres), con una mediana de edad de 66 años. La localización y estadios más frecuentes fueron colon derecho (18 casos, 41,9 %); y IIIA, IIIB, respectivamente. La resecabilidad de la serie fue 100 %. La medianas del tiempo quirúrgico, del número de linfonodos resecados y de estancia hospitalaria; fueron de 100 minutos, 30 y 5 días, respectivamente. La MPO fue 30,2 % (13 casos). Con una mediana de seguimiento de 55 meses, se verificó una recurrencia de 13,9 %; y SVAG a 5 años de 69,8 % para la totalidad de la serie. Los resultados obtenidos, en términos de MPO, mortalidad y SVAG a 5 años, fueron similares a series de nacionales e internacionales.

The standard treatment of colonic cancer (CC) continues to be the radical resection of the intestinal segment compromised with free margins, associated or not with adjuvant therapies. The aim of this study was to determine postoperative morbidity (POM) and 5-year overall survival (OS) in patients resected by non-complicated CC. The methodology used was a series of cases in retrospective of patients with non-complicated CC undergoing colectomy and lymphadenectomy, consecutively, at RedSalud Mayor Temuco Clinic, between 2007 and 2017. The outcome variable was 5-years OS. Other variables of interest were: surgical time, the number of resected lymph nodes, hospital stay, POM, and recurrence. Patients were followed clinically. Descriptive statistics were used (measures of central tendency and dispersion), and OS analysis was applying Kaplan Meier curves. 43 patients (58.1% men) were intervened, with a median age of 66 years. The most frequent localization and stages were the right colon (18 cases, 41.9%); and IIIA, IIIB respectively. Median surgical time, the number of resected lymph nodes and hospital stay were 100 min, 30 and 5 days respectively. MPO was 30.2% (13 cases). With a median follow-up of 55 months, a recurrence of 13.9% was verified, and a 5-year OS of 69.8% was observed. The results, in terms of POM, mortality and 5-year OS, were similar to the national and international series.

Structure-Activity Relationship Analysis on Antioxidant and Anticancer Actions of Theaflavins on Human Colon Cancer Cells.

The roles of natural products as effective cancer prevention and therapeutic agents have been documented by various studies in recent years, but the action mechanisms and structure-activity relationship need more elucidation. The present study showed that theaflavins (theaflavin and its derivatives, TFs) from black tea caused an inhibitory effect on the proliferation of human colon adenocarcinoma cancer SW480 cells and human colon cancer SW620 cells [half maximal inhibitory concentration (IC50) < 32.0 µM] by the induction of cell cycle arrest but exerted lower toxicity against normal cells with a high safety index (1.89-6.26). Moreover, TFs triggered a decrease in reactive oxygen species in SW480 cells as a result of their excellent radical-scavenging ability (e.g., the IC50 value of TF4 to ABTS• + was 1.91 ± 0.21 µM). More importantly, the structure-activity relationship analysis of TFs exhibited that the galloyl group was an important factor to affect these activities. Taken together, we revealed that the TFs could act as substitutes for natural antioxidants and promising anticancer agents with beneficial influence on human health and then anticipated that this study may provide useful information on the development of therapeutic natural products.

Induction of Apoptosis and Cell-Cycle Arrest in Human Colon-Cancer Cells by Whole-Grain Alkylresorcinols via Activation of the p53 Pathway.

Colon cancer, one of the leading causes of cancer-associated deaths, is the target of choice for nutrition-based-prevention approaches because of the direct and early contact between the active compounds and the cancerous tissues. We previously reported alkylresorcinols (ARs) as the major active components in wheat bran against human colon cancer. Here, we further investigate the anticancer mechanisms of action of ARs. Our mechanistic studies indicated that AR C15 and AR C17 exert their anticancer activities in colon-cancer cells by inducing apoptosis through PUMA upregulation and mitochondrial-pathway activation, inducing cell-cycle arrest through p21 upregulation, and inhibiting proteasome activity and Mdm2 expression. This cascade of distinct mechanisms was linked to the consequent activation and accumulation of p53. The results of treatment with p53 inhibitor further confirmed that the p53 pathway might play a very important role in AR-induced apoptosis in colon-cancer cells. Altogether these results show that AR C15 and AR C17 can specifically activate the mitochondrial pathway of apoptosis and cause cell-cycle arrest and that inhibition of p53 greatly reduces the activation of this pathway.

Chemopreventive effects of some popular phytochemicals on human colon cancer: a review.

Colon cancer is one of the major causes of morbidity and mortality worldwide. Dietary phytochemicals have been drawing increasing attention for colon cancer prevention and treatment due to their chemical diversity, biological activity, easy availability, lack of toxic effects, and ability to modulate various signal transduction pathways and cell processes. The chemoprotective effects elicited by phytochemicals include antioxidative and anti-inflammatory activities, induction of phase II enzymes, cell cycle arrest, apoptosis, autophagy, and changes in gut microbiota. The present review summarizes the main chemopreventive properties of selected phytochemicals (carotenoids, flavonoids, flavonolignan, proanthocyanidin, isothiocyanates, terpenoids, peptides, and medicinal plant extracts) against colon cancer. It is found that these phytochemicals exhibit their anti-colon cancer activity through the modulation of various signaling pathways involved in the regulation of chronic inflammation, cell cycle, autophagy, apoptosis, metastasis, and angiogenesis. These phytochemicals could be helpful starting points in the design and development of novel colon cancer chemopreventive agents.

Avenanthramide Aglycones and Glucosides in Oat Bran: Chemical Profile, Levels in Commercial Oat Products, and Cytotoxicity to Human Colon Cancer Cells.

Avenanthramides (AVAs), unique phytochemicals in oat, have attracted an increasing amount of attention due to their outstanding health benefits. However, the chemical profile and the levels of AVAs in commercial oat products as well as their health benefits have not been examined in detail. In the present study, a total of 29 AVA aglycones and AVA glucosides were identified and characterized from oat bran using NMR (1D and 2D NMR) and LC-MS techniques. Among them, 17 novel AVA glucosides were reported in oat bran for the first time. The most abundant AVA glucoside, 2c-3'- O-glc, had a similar growth inhibitory activity with the major AVA, 2c, against HCT-116 and HT-29 human colon cancer cells, indicating glucosylation does not affect the growth inhibitory effects of AVAs. Furthermore, the levels of all individual AVAs in 13 commercial oat products were analyzed using HPLC-MS/MS. The total AVAs contents in various oat products ranged from 9.22 to 61.77 mg/kg (fresh weight).