mangostin has been researched along with Colonic-Neoplasms* in 10 studies
10 other study(ies) available for mangostin and Colonic-Neoplasms
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Alpha-mangostin and resveratrol, dual-drugs-loaded mucoadhesive thiolated chitosan-based nanoparticles for synergistic activity against colon cancer cells.
Alpha-mangostin (M) and resveratrol (R), dual-drugs-loaded mucoadhesive thiolated chitosan-based nanoparticles (NPs) coated by Eudragit® S100 (S) were developed for colon-specific delivery and synergistic activity against colon cancer cells. The NPs were prepared by the ionotropic gelation method and coated with S. The particle size and zeta potential of NPs before and after the coating process were observed. The M and R loading efficiency, mucoadhesive properties, as well as release patterns were examined. Moreover, the activity against colon cancer cells of M, R, and NPs were studied for their synergistic activity. M and R-loaded NPs (MR-TNPs) were spherical in shape with sizes of around 540 nm and zeta potential of +39 mV. The S coating of MR-TNPs provided larger particle sizes which offered lower zeta potential. However, it created an increase in M and R loading, prevented M and R release at the upper gastrointestinal tract, and enhanced M and R reaching the colon. S dissolved at pH > 7.0 while thiolated chitosan formed the mucoadhesion, resulting in M and R remaining in the colon and allowing them to enter the colon cancer cells. The half-maximal inhibitory concentration values of NPs was dramatically decreased when M and R were dually loaded into the NPs, which indicated significantly higher activity against colon cancer cells. Moreover, M and R loading at this ratio applied synergistic efficiency. The results illustrated that NPs successfully loaded drugs and achieved synergistic efficiency. This system could be promising in facilitating targeted nanomedicines for the treatment of colon cancer. Topics: Chitosan; Colonic Neoplasms; Drug Carriers; Humans; Nanoparticles; Particle Size; Resveratrol; Xanthones | 2022 |
Suppressive effect of α-mangostin for cancer stem cells in colorectal cancer via the Notch pathway.
Since colon cancer stem cells (CSCs) play an important role in chemoresistance and in tumor recurrence and metastasis, targeting of CSCs has emerged as a sophisticated strategy for cancer therapy. α-mangostin (αM) has been confirmed to have antiproliferative and apoptotic effects on cancer cells. This study aimed to evaluate the selective inhibition of αM on CSCs in colorectal cancer (CRC) and the suppressive effect on 5-fluorouracil (5-FU)-induced CSCs.. The cell viability assay was performed to determine the optimal concentration of αM. A sphere forming assay and flow cytometry with CSC markers were carried out to evaluate the αM-mediated inhibition of CSCs. Western blot analysis and quantitative real-time PCR were performed to investigate the effects of αM on the Notch signaling pathway and colon CSCs. The in vivo anticancer efficacy of αM in combination with 5-FU was investigated using a xenograft mouse model.. αM inhibited the cell viability and reduced the number of spheres in HT29 and SW620 cells. αM treatment decreased CSCs and suppressed the 5-FU-induced an increase in CSCs on flow cytometry. αM markedly suppressed Notch1, NICD1, and Hes1 in the Notch signaling pathway in a time- and dose-dependent manner. Moreover, αM attenuated CSC markers CD44 and CD133, in a manner similar to that upon DAPT treatment, in HT29 cells. In xenograft mice, the tumor and CSC makers were suppressed in the αM group and in the αM group with 5-FU treatment.. This study shows that low-dose αM inhibits CSCs in CRC and suppresses 5-FU-induced augmentation of CSCs via the Notch signaling pathway. Topics: Animals; Cell Line, Tumor; Colonic Neoplasms; Humans; Mice; Neoplasm Recurrence, Local; Neoplastic Stem Cells; Xanthones | 2022 |
Mucoadhesive chitosan and thiolated chitosan nanoparticles containing alpha mangostin for possible Colon-targeted delivery.
α-Mangostin-loaded mucoadhesive nanoparticles (NPs) were prepared for colon-targeted drug delivery against colorectal cancer cells using pH-dependent composite mucoadhesive NPs. Chitosan (CS) and thiolated chitosan (TCS) were used to form the NPs, following by genipin (GP) crosslinking and the surface modification by Eudragit Topics: Antineoplastic Agents; Chitosan; Colon; Colonic Neoplasms; Drug Carriers; Drug Delivery Systems; HT29 Cells; Humans; Nanoparticles; Protein Kinase Inhibitors; Sulfhydryl Compounds; Xanthones | 2021 |
Understanding of tolerance in TRAIL-induced apoptosis and cancelation of its machinery by α-mangostin, a xanthone derivative.
Tumor necrosis-factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF-superfamily that selectively induces apoptosis through death receptors (DRs) 4 and/or 5 in cancer cells. These receptors are expressed on the cancer cell surface, without affecting normal cells. Unfortunately, many clinical studies have shown that cancer cells acquire TRAIL-resistance and finally avoid TRAIL-induced apoptosis. The detailed mechanisms of this resistance are not well understood. In the current study, we established a TRAIL-resistant human colon cancer DLD-1 cell line to clarify the mechanisms of TRAIL-resistance and developed agents to cancel its machinery. Also, we found that cancer stem-like cells from breast epithelial proliferating MCF10A cells were also sensitive to TRAIL-induced apoptosis. The enforced expression of DR5 in both TRAIL-resistant cells partially recovered the sensitivity to the TRAIL ligand, which was judged by the activation of caspase-8. As a result, we newly found that the mechanisms of TRAIL-resistance comprised co-existence of a decrease in the expression level of DR5 along with malfunction of its recruitment to the cell surface, as evidenced by Western blot and immunocytological analysis, respectively. Interestingly, α-mangostin, which is a xanthone derivative, canceled the resistance by increasing the expression level of DR5 through down-regulation of miR-133b and effectively induced the translocation of DR5 to the cancer cell surface membrane in TRAIL-resistant DLD-1 cells. These findings indicate that α-mangostin functioned as a sensitizer of TRAIL-induced apoptosis and may thus serve as a possible adjuvant compound for cytokine therapy to conquer TRAIL-resistance. Topics: Antineoplastic Agents; Apoptosis; Breast Neoplasms; Caspase 8; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Enzyme Activation; Female; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Neoplastic Stem Cells; Protein Transport; Receptors, TNF-Related Apoptosis-Inducing Ligand; RNA Interference; Signal Transduction; TNF-Related Apoptosis-Inducing Ligand; Transfection; Xanthones | 2015 |
Anti-cancer effects of naturally occurring compounds through modulation of signal transduction and miRNA expression in human colon cancer cells.
Much evidence indicates that various naturally occurring compounds have an anti-cancer effect, but the detailed mechanisms are not well understood. In this study, we selected anti-cancer phytochemicals such as epigallocatechin-3-gallate (EGCG), resveratrol (RES) and α-mangostin (α-M), all of which are well-characterized chemopreventive agents. We sought to elucidate the mechanism of their anti-cancer effects and the synergistic effects obtained by combined treatment with the anti-cancer drug 5-fluorouracil (5-FU) in three human colon cancer cell lines. The numbers of viable cells were consistently decreased by the treatment with EGCG, RES or α-M at more than 10 μM in all three cell lines tested. All compounds mainly induced apoptosis and suppressed the PI3K/Akt signaling pathway. Additionally, α-M, which had the greatest PI3K/Akt-suppressing activity, also suppressed MAP kinase (MAPK)/Erk1/2 signaling. Importantly, the combination treatment with RES and 5-FU induced a remarkably synergistic enhancement of growth inhibition and apoptosis through the additional suppression of the MAPK/Erk1/2 signaling pathway in colon cancer DLD-1 cells. Interestingly, RES increased the intracellular expression level of miR-34a, which down-regulated the target gene E2F3 and its downstream Sirt1, resulting in growth inhibition. These findings indicate that these compounds functioned as chemosensitizers when combined with anti-cancer drugs through the modulation of apoptotic and growth-related signaling pathways. Also, RES exerted its anti-cancer activity in part through a newly defined mechanism, i.e., the miR-34a/E2F3/Sirt1 cascade. Topics: Antineoplastic Agents; Apoptosis; Catechin; Cell Line, Tumor; Colonic Neoplasms; Drug Resistance, Neoplasm; Humans; MicroRNAs; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Phosphatidylinositol 3-Kinases; Resveratrol; Signal Transduction; Stilbenes; Xanthones | 2013 |
In vivo toxicity and antitumor activity of mangosteen extract.
Mangosteen (Garcinia mangostana) has been widely used in the traditional medicine of Thailand to treat various ailments, especially diseases of the digestive system and infections. Many reports show antiproliferation of crude extracts and active constituents from mangosteen against many cancer cell lines. Therefore, the current study is proposed to demonstrate in vivo evidence on the antitumor activity of mangosteen. Crude methanolic extract (CME) from mangosteen pericarp including 25.19 % α-mangostin as an active xanthone was used in this study. The inhibition on tumor cell proliferation of CME was preliminarily evaluated against the murine colon cancer cell line NL-17 with an IC50 value of 17 and 84 μg/ml based on WST-1 and LDH assays, respectively. The safety dose for animal application was assessed by in vivo toxicity studies using female BALB/c mice. Acute toxicity showed an LD50 value and approximate lethal dose at 1,000 mg/kg, whereas the suitable dose for short-term study should be ≤200 mg/kg. The effective dose for antitumor activity of CME was found to be between 100 and 200 mg/kg, with a tumor size reduction of 50-70 %. Histological staining clearly illustrated a decrease of tumor cell density in the footpad in a dose-dependent manner. The median survival time and life span significantly increased in tumor-bearing mice with CME treatment. This study suggests that CME possesses a powerful antitumor activity. Therefore, it is worth undertaking further investigation to identify active compounds and obtain a deeper understanding of their mechanism, in order to acquire novel effective anticancer drugs. Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Chromatography, High Pressure Liquid; Colonic Neoplasms; Female; Fruit; Garcinia mangostana; Mice; Mice, Inbred BALB C; Plant Extracts; Xanthones | 2013 |
Anti-tumorigenicity of dietary α-mangostin in an HT-29 colon cell xenograft model and the tissue distribution of xanthones and their phase II metabolites.
This study investigated the in vivo and in vitro activity of α-mangostin (α-MG), the most abundant xanthone in mangosteen pericarp, on HT-29 cell tumorigenicity, proliferation, and several markers of tumor cell activity, as well as the profile and amounts of xanthones in serum, tumor, liver, and feces.. Balb/c nu/nu mice were fed either control diet or diet containing 900 mg α-MG/kg. After 1 week of acclimation to diet, mice were injected subcutaneously with HT-29 cells and fed the same diets ad libitum for an additional 2 or 4 weeks. After 2 and 4 weeks, tumor mass and the concentrations of BcL-2 and β-catenin in tumors of mice fed diet with α-MG were significantly less than in mice fed control diet. Xanthones and their metabolites were identified in serum, tumor, liver, and feces. In vitro treatment of HT-29 cells with α-MG also inhibited cell proliferation and decreased expression of BcL-2 and β-catenin.. Our data demonstrate that the anti-neoplastic effect of dietary α-MG is associated with the presence of xanthones in the tumor tissue. Further investigation of the impact of beverages and food products containing xanthones on the prevention of colon cancer or as complementary therapy is merited. Topics: Animals; Antineoplastic Agents; beta Catenin; Beverages; Biomarkers; Cell Proliferation; Cell Survival; Colonic Neoplasms; Diet; Female; HT29 Cells; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Proto-Oncogene Proteins c-bcl-2; Tissue Distribution; Xanthones; Xenograft Model Antitumor Assays | 2013 |
Gamma-mangostin, a micronutrient of mangosteen fruit, induces apoptosis in human colon cancer cells.
Recently colorectal cancer rates have increased rapidly in Taiwan. The treatment of colorectal cancer includes surgery, radiation therapy and chemotherapy. Mangosteen (Garcinia mangostana) is a famous Asian tropical fruit. γ-Mangostin is a xanthone derivative isolated from the fruit hull. In previous studies, we found evidence of anti-inflammatory and anti-brain tumor activities in γ-mangostin. In this study, we performed further studies to assess the apoptotic effects of γ-mangostin on colorectal adenocarcinoma cells HT29. γ-Mangostin showed concentration and time-dependent cytotoxic effects on HT29 cells. Microscopic observation under Giemsa staining showed that γ-mangostin induced cellular swelling and the appearance of apoptotic bodies, characteristic of apoptosis in HT29 cells. In addition, flow cytometry analysis showed an increase of hypodiploid cells in γ-mangostin-treated HT29 cells, while enhancement of intracellular peroxide production was detected in the same γ-mangostin-treated cells by DCHDA assay and DiOC6(3) staining. In view of the above results, γ-mangostin has demonstrated anticancer activity and induces apoptosis in HT29 colorectal adenocarcinoma cells. The evidence suggests that γ-mangostin could serve as a micronutrient for colon cancer prevention and is a potential lead compound for the development of anti-colon cancer agents. Topics: Apoptosis; Catalase; Cell Proliferation; Cell Shape; Colonic Neoplasms; Diploidy; Drug Screening Assays, Antitumor; Fruit; Garcinia mangostana; HT29 Cells; Humans; Intracellular Space; Micronutrients; Mitochondria; Mitochondrial Membranes; Peroxides; Phytotherapy; Time Factors; Xanthones | 2012 |
Effects of α-mangostin on apoptosis induction of human colon cancer.
To investigate the effect of α-mangostin on the growth and apoptosis induction of human colon cancer cells.. The three colorectal adenocarcinoma cell lines tested (COLO 205, MIP-101 and SW 620) were treated with α-mangostin to determine the effect on cell proliferation by MTT assay, cell morphology, chromatin condensation, cell cycle analysis, DNA fragmentation, phosphatidylserine exposure and changing of mitochondrial membrane potential. The molecular mechanisms of α-mangostin mediated apoptosis were further investigated by Western blotting analysis including activation of caspase cascade, cytochrome c release, Bax, Bid, p53 and Bcl-2 modifying factor.. The highest inhibitory effect of α-mangostin on cell proliferation of COLO 205, MIP-101 and SW 620 were 9.74 ± 0.85 μg/mL, 11.35 ± 1.12 μg/mL and 19.6 ± 1.53 μg/mL, respectively. Further study showed that α-mangostin induced apoptotic cell death in COLO 205 cells as indicated by membrane blebbing, chromatin condensation, DNA fragmentation, cell cycle analysis, sub-G1 peak (P < 0.05) and phosphatidylserine exposure. The executioner caspase, caspase-3, the initiator caspase, caspase-8, and caspase-9 were expressed upon treatment with α-mangostin. Further studies of apoptotic proteins were determined by Western blotting analysis showing increased mitochondrial cytochrome c release, Bax, p53 and Bmf as well as reduced mitochondrial membrane potential (P < 0.05). In addition, up-regulation of tBid and Fas were evident upon treatment with α-mangostin (P < 0.01).. α-Mangostin may be effective as an anti-cancer agent that induced apoptotic cell death in COLO 205 via a link between extrinsic and intrinsic pathways. Topics: Apoptosis; Caspases; Cell Cycle; Cell Line, Tumor; Cell Survival; Colonic Neoplasms; Cytochromes c; DNA Fragmentation; Enzyme Activation; Humans; Protein Kinase Inhibitors; Xanthones | 2011 |
Xanthones induce cell-cycle arrest and apoptosis in human colon cancer DLD-1 cells.
We investigated the antiproliferative effects of four structurally similar prenylated xanthones, alpha-mangostin, beta-mangostin, gamma-mangostin, and methoxy-beta-mangostin, in human colon cancer DLD-1 cells. These xanthones differ in the number of hydroxyl and methoxy groups. Except for methoxy-beta-mangostin, the other three xanthones strongly inhibited cell growth at 20 microM and their antitumor efficacy was correlated with the number of hydroxyl groups. Hoechst 33342 nuclear staining and nucleosomal DNA-gel electrophoresis revealed that the antiproliferative effects of alpha- and gamma-mangostin, but not that of beta-mangostin, were associated with apoptosis. It was also shown that their antiproliferative effects were associated with cell-cycle arrest by affecting the expression of cyclins, cdc2, and p27; G1 arrest was by alpha-mangostin and beta-mangostin, and S arrest by gamma-mangostin. These findings provide a relevant basis for the development of xanthones as an agent for cancer prevention and combination therapy with anti-cancer drugs. Topics: Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; G1 Phase; Humans; Molecular Structure; S Phase; Xanthones | 2005 |