tocotrienol--delta and Colonic-Neoplasms

Topics: Animals; Antineoplastic Agents; Azoxymethane; Benzopyrans; Carcinogenesis; Colitis; Colonic Neoplasms; Dextran Sulfate; Fatty Acids; Feces; Gastrointestinal Microbiome; Humans; Inflammation; Interleukin-1beta; Male; Mice; Mice, Inbred BALB C; RNA, Ribosomal, 16S; Vitamin E

The genus Tabernaemontana has widespread distribution throughout tropical and subtropical parts of the world, i.e. Africa, Asia and America which has long been used for treatments of different disease conditions including tumours, wounds, syphilis, stomach ache and headache. Some Tabernaemontana species are used for treatment of piles, spleen and abdominal tumours in India. In particular, the leaf of Tabernaemontana corymbosa is used for treatment of tumours in Bangladesh. Parts of the plant or whole plants are used as decoctions, steam bath, powder and ointments.. The present study was undertaken to study the mechanism of apoptosis induction in human glioblastoma (U87MG) and colorectal adenocarcinoma (HT-29) cancer cells by a novel indole alkaloid, jerantinine B isolated from T. corymbosa, δ-tocotrienol and the combined low-dose treatments of δ-tocotrienol with IC20 dose of jerantinine B.. Cell viability, isobologram and combinational index (CI) analyses were used to determine the pharmacological interaction between combined treatments based on the IC50 values obtained. Fluorescence and histochemical staining techniques as well as comet assay were used for evaluating the morphological changes and DNA damage pattern, respectively. The effects of treatments on microtubules, caspase activity and cell death were determined using immunofluorescence technique, caspase colorimetric and neutral red uptake assays, respectively.. Jerantinine B, δ-tocotrienol and combined low-dose treatments induced a dose-dependent growth inhibition against U87MG and HT-29 cells selectively with less toxicity acted towards the normal MRC5 cells. Synergistic growth inhibition observed with CI values of 0.85 and 0.77 for U87MG and HT-29 cells, resulting in up to 2-fold and 3.8-fold dose reduction of δ-tocotrienol and jerantinine B, respectively. U87MG and HT-29 cells exhibited morphological features of apoptosis and double stranded DNA breaks. Individual and combined treatments induced caspase 8 and 3 activities and cell death independent of caspase activation on U87MG and HT-29 cells. An increased caspase 9 activity was also evident on U87MG and HT-29 treated with combined treatments and HT-29 cells treated with jerantinine B. Jerantinine B and combined low-dose treatments with δ-tocotrienol undoubtedly disrupted the microtubule networks.. The present study demonstrated the mechanism for cytotoxic potency of δ-tocotrienol and jerantinine B against U87MG and HT-29 cells. Furthermore, combined low-dose treatments induced concurrent synergistic inhibition of cancer cell growth with concomitant dose reduction thus minimizing toxicity to normal cells and improving potency of δ-tocotrienol and jerantinine B.

Topics: Antineoplastic Agents; Brain Neoplasms; Caspases; Cell Line; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colonic Neoplasms; DNA Damage; Drug Synergism; Humans; Indole Alkaloids; Tabernaemontana; Vitamin E

Based on the antitumor function of the delta-tocotrienol, shed light on the relationship between the proliferation inhibition effect of delta-tocotrienol on human colon cancer cells SW620 with Wnt signal pathway.. To adopt the MTT method, found the effects of diverse doses of delta-tocotrienol on colon cancer cells SW620. Detected the expressions level of the factors related to Wnt signal pathway via Western bloting and immunocytochemistry, to observe the influence of delta-tocotrienol on Wnt-1, beta-catenin, c-jun, cylin D1.. delta-tocotrienol has a significant proliferation inhibition effect on the colon cancer cells SW620,under delta-tocotrienol treated, SW620 cell inhibition rate is 70.43%. The IC50 is 15.18 micromol/L. The expression levels of wnt-1, beta-catenin c-jun and cylin D1 are downregulated (P < 0.05).. The proliferation inhibition effect of delta-tocotrienol on colon cancer cell may correlate with the ability of delta-tocotrienol to downregulate the expression levels of wnt-1, beta-catenin, c-jun, cylin D1 in the Wnt signal pathway.

Topics: beta Catenin; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Cyclin D1; Down-Regulation; Humans; Proto-Oncogene Proteins c-jun; Vitamin E; Wnt Signaling Pathway; Wnt1 Protein

Tocotrienol is considered a beneficial effect agent on inhibition of tumor development. In this study, we focused on the effects of δ-tocotrienol and its possible mechanism on induction of death in human colon cancer SW620 cells. δ-Tocotrienol inhibited proliferation of SW620 cell in a dose-dependent manner. Our findings showed that δ-tocotrienol effectively induced paraptosis-like death in SW620 cells, correlated with the vacuolation that may be from welling and fusion of mitochondria and/or the endoplasmic reticulum (ER) as well as caspase-3 nonactivated. However, there were no changes in apoptosis based on flow cytometry analysis. Of being noted, δ-tocotrienol reduced the expression of β-catenin and wnt-1 proteins by about 50% at the highest dose (20μmol/L). δ-Tocotrienol also decreased cyclin D1, c-jun and MMP-7 protein levels in SW620 cells. Altogether, these data indicate that δ-tocotrienol induces paraptosis-like cell death, which is associated with the suppression of the Wnt signaling pathway. Thus, our findings may provide a novel application in treatment of human colon carcinoma.

Topics: Apoptosis; Caspase 3; Cell Death; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Dose-Response Relationship, Drug; Flow Cytometry; Humans; Mitochondria; Signal Transduction; Vitamin E; Wnt Proteins; Wnt1 Protein