tannins and Colorectal-Neoplasms

Colorectal cancer is the third most common malignancy that leads to significant mortality around the world. Chronic colonic inflammation could induce a protumor effect by the massive release of pro-inflammatory cytokines, facilitating migration, invasion, and metastasis of malignant cells in colorectal cancer. Therefore, developing a combination regimen of anti-inflammation and antitumor therapies is a promising strategy for the treatment of colorectal cancer. Here, we report that tannic acid-containing nanoparticles, formed by a turbulent-mixing technique, have exhibited uniform size, high stability, and pH-triggered drug release in the gastrointestinal tract, and could overcome intestinal mucosa for drug delivery in the colorectal region. As a drug carrier itself, with potent antioxidant and anti-inflammatory properties, tannic acid-containing nanoparticles showed great therapeutic effect in preventing the development of colitis-associated colorectal cancer (CAC) through oral administration. Furthermore, we used a therapeutic nanocarrier to deliver chemotherapeutic drugs for CAC treatment, generating lower systemic toxicity and superior antitumor performance through concurrent anti-inflammation and antitumor treatment. As a result, we confirmed that the drug carrier itself with therapeutic function could improve the overall therapeutic performance, and provided a safe and effective tannic acid-containing nanoplatform for the prevention and treatment of colon diseases.

Topics: Anti-Inflammatory Agents; Colitis; Colorectal Neoplasms; Drug Carriers; Humans; Inflammation; Nanoparticles; Polyphenols; Tannins

Despite the medico-surgical progress that has been made in the management of patients with colorectal cancer (CRC), the prognosis at five years remains poor. This resistance of cancer cells partly results from their phenotypic characteristics in connection with the epithelial-mesenchymal transition (EMT). In the present study, we have explored the ability of a polyphenol, tannic acid (TA), to counteract CRC cell proliferation and invasion through an action on the EMT. We highlight that TA decreases human SW480 and SW620 CRC cell and murine CT26 CRC cell viability, and TA inhibits their adhesion in the presence of important factors comprising the extracellular matrix, particularly in the presence of collagen type I and IV, and fibronectin. Moreover, these properties were associated with TA's ability to disrupt CRC cell migration and invasion, which are induced by transforming growth factor-β (TGF-β), as evidence in the video microscopy experiments showing that TA blocks the TGF-β1-induced migration of SW480 and CT26 cells. At the molecular level, TA promotes a reversal of the epithelial-mesenchymal transition by repressing the mesenchymal markers (i.e., Slug, Snail, ZEB1, and N-cadherin) and re-expressing the epithelial markers (i.e., E-cadherin and β-catenin). These effects could result from a disruption of the non-canonical signaling pathway that is induced by TGF-β1, where TA strongly decreases the phosphorylation of extracellular-signal regulated kinase ERK1/2, P38 and the AKT proteins that are well known to contribute to the EMT, the cell motility, and the acquisition of invasive properties by tumor cells. Very interestingly, a preclinical study of mice with subcutaneous murine tumor colon CT26 cells has shown that TA was able to significantly delay the growth of tumors without hepato- and nephrotoxicities.

Topics: Animals; Cadherins; Colorectal Neoplasms; Epithelial-Mesenchymal Transition; Humans; Hydrolyzable Tannins; Mice; Tannins; Transforming Growth Factor beta; Transforming Growth Factor beta1; Transforming Growth Factors

Seaweeds are one of the largest producers of biomass in the marine environment and a source of multiple bioactive metabolites with valuable health benefits. Among these, phlorotannins have been widely recognized for their promising bioactive properties. The potential antitumor capacity of

Topics: Apoptosis; Caco-2 Cells; Cell Line, Tumor; Chromatography, High Pressure Liquid; Colorectal Neoplasms; Flow Cytometry; Fucus; Gastrointestinal Tract; Humans; Plant Extracts; Seaweed; Signal Transduction; Stomach Neoplasms; Tannins

The tannase-producing Gram-positive bacterial species Streptococcus gallolyticus subsp. gallolyticus (Sgg) is an opportunistic pathogen of the human gut and strongly associated with colorectal cancer (CRC). A unique feature of Sgg is its ability to degrade tannic acids (TA). TA constitute an important part of the human diet with known anti-tumorigenic properties. Here, we examined whether Sgg is able to protect tumor cells from the toxic effect of TA and thus drive tumorigenesis indirectly. Human CRC cell lines (n = 8) were treated with increasing concentrations of TA. We confirmed the cytotoxic activity of TA in a dose-dependent manner. In virtually all cell lines, viability decreased significantly (>60% inhibition). Moreover, pyrogallol, the degradation product of TA, had no effect on the tested cell lines. This suggests a specific effect of TA. Cytotoxicity was due to necrosis and induction of senescence in residual cells. Finally, when TA was degraded by Sgg, the cytotoxic effect could be abolished. Tumor cells even responded with boosted cell proliferation, highlighting the impact of Sgg on CRC progression. We here provide another piece of evidence for the active interplay between Sgg and cancer preventive components. These data will help to move forward in designing concepts for therapeutic and eventually also prophylactic approaches to combat gastrointestinal malignancies.

Topics: Antineoplastic Agents; Biotransformation; Carcinogenesis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Colorectal Neoplasms; Dose-Response Relationship, Drug; Humans; Neoplasm Invasiveness; Phytotherapy; Streptococcus gallolyticus; Streptococcus gallolyticus subspecies gallolyticus; Tannins

Tannic acid, a hydrolysable tannin, exists commonly in food plants. Tannic acid has already been shown various anticancer mechanisms such as inhibiting the proliferation, inducing a higher apoptotic rate and slowing down the metastasis of different cancers. Moreover, tannic acid was reported to reduce the side effects caused by chemotherapeutics on patients. But whether the tannic acid can improve the treatment of oxaliplatin on colorectal carcinomatosis has yet been studied. In this study, we developed an injectable drug delivery system by physical incorporation of oxaliplatin (OXA) and tannic acid (TA) polymeric nanoparticles (OXA/TA NPs) into a thermo-sensitive hydrogel, OXA/TA NPs-hydrogel (OXA/TA NPs-H). The OXA/TA NPs-H was injected into the peritoneal cavity for the treatment of colorectal peritoneal carcinoma. Firstly, a water-in-oil-in-water double-emulsion (w/o/w) method and solvent-evaporation procedure were used in the preparation of the biodegradable OXA/TA NPs. Then, we prepared the biodegradable thermo-sensitive poly(3-caprolactone) (PCL)-10R5-PCL (PCLR) hydrogel with a low critical solution temperature (LCST) which undergoes gelation process at body temperature. Transmission electron microscopy (TEM) showed the spherical profile of OXA/TA NPs. Fourier-transform infrared (FTIR) spectra demonstrated that OXA and TA were both encapsulated into the OXA/TA NPs. In this study, intraperitoneal application of OXA/TA NPs-H restricted the growth of CT26 peritoneal colon cancer in vivo, improved the quality of life and prolonged the survival time of the model mice. Our study suggested that OXA/TA NPs-H might have potential application in the treatment of colorectal cancer.

Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Survival; Colorectal Neoplasms; Hydrogels; Male; Mice; Mice, Inbred BALB C; Nanoparticles; Neoplasms, Experimental; Oxaliplatin; Specific Pathogen-Free Organisms; Tannins; Temperature

Colorectal cancer, which is the third most common type of cancer diagnosed in both men and women, is the leading cause of cancer-related deaths worldwide. Cowanin is a pure compound extracted from Garcinia cowa Roxb., a tree species present in Thailand, Malaysia and Myanmar. The crude extract has been demonstrated to have antitumor activity, inflammation induction, antibacterial activity, anti-inflammatory activity and antimalarial activity. In the present study, the effects of cowanin on apoptosis induction and on the apoptosis-related and mitogen-activated protein kinase (MAPK) pathways were investigated in the LoVo human colorectal cancer cell line. The cytotoxicity of cowanin in LoVo cells was determined by MTT assay. Hoechst 33342 and JC‑1 staining were used to determine nuclear morphological changes and mitochondrial membrane potential, respectively. The expression levels of BCL2 apoptosis regulator (Bcl‑2) family, MAPK and AKT serine/threonine kinase 1 (Akt) pathway proteins following cowanin treatment were determined by western blot analysis. The results demonstrated that cowanin inhibited cell proliferation and induced cell death via the apoptosis pathway. Cowanin treatment increased BCL2 associated X (Bax) and decreased Bcl‑2 expression. In addition, cowanin activated caspase‑9, -7 and poly-ADP-ribose-polymerase expression. Furthermore, cowanin decreased the levels of phosphorylated extracellular signal-regulated kinase (p‑ERK), p‑Akt, p‑3‑phosphoinositide‑dependent protein kinase‑1, while it increased p‑p38 expression, thus resulting in the induction of apoptosis. In conclusion, cowanin inhibited cell proliferation and induced apoptosis of LoVo cells via the MAPK and Akt signaling pathways. Notably, inhibition of p38 by using a p38 inhibitor (SB203580) prevented the cowanin-induced apoptosis in LoVo cells. These results suggested that cowanin may be a potential candidate for the treatment of colorectal cancer and provided important information on the molecular mechanisms underlying its antitumor activity.

Topics: Caspase 7; Caspase 9; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colorectal Neoplasms; Gene Expression Regulation, Neoplastic; Humans; Imidazoles; MAP Kinase Signaling System; p38 Mitogen-Activated Protein Kinases; Poly(ADP-ribose) Polymerases; Proto-Oncogene Proteins c-akt; Pyridines; Tannins

The Western diet (WD) is associated with a higher incidence of colorectal cancer (CRC) than the Mediterranean diet. Polyphenols extracted from Annurca apple showed chemopreventive properties in CRC cells. A multifactorial, four-arm study by using wild-type (wt) and Apc(Min/+) mice was carried out to evaluate the effect on polyp number and growth of APE treatment (60 μmol/L) ad libitum in drinking water combined with a WD or a balanced diet (BD) for 12 weeks. Compared with APE treatment, we found a significant drop in body weight (P < 0.0001), severe rectal bleeding (P = 0.0076), presence of extraintestinal tumors, and poorer activity status (P = 0.0034) in water-drinking Apc(Min/+) mice, more remarkably in the WD arm. In the BD and WD groups, APE reduced polyp number (35% and 42%, respectively, P < 0.001) and growth (60% and 52%, respectively, P < 0.0001) in both colon and small intestine. Increased antioxidant activity was found in wt animals fed both diets and in Apc(Min/+) mice fed WD and drinking APE. Reduced lipid peroxidation was found in Apc(Min/+) mice drinking APE fed both diets and in wt mice fed WD. In normal mucosa, mice drinking water had lower global levels of DNA methylation than mice drinking APE. APE treatment is highly effective in reducing polyps in Apc(Min/+) mice and supports the concept that a mixture of phytochemicals, as they are naturally present in foods, represent a plausible chemopreventive agent for CRC, particularly in populations at high risk for colorectal neoplasia.

Topics: Adenomatous Polyposis Coli Protein; Animals; Chlorogenic Acid; Colorectal Neoplasms; Diet; Disease Models, Animal; DNA Methylation; Drinking; Female; Flavonoids; Intestinal Polyps; Lipid Peroxidation; Male; Mice; Mice, Inbred C57BL; Phenols; Polyphenols; Tannins