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Background and purpose: Today, despite the abundance of chemical drugs, the use of medicinal plants is increasing; Curcumin (curcumin) is a yellow pigment obtained from the turmeric plant and is considered the effective ingredient of turmeric. This crystalline and crystallized product is widely used in Indian medicine. Recently, the beneficial effects of curcumin on stomach, colon, and mouth cancers have been proven in mice. Curcumin usually plays its role through pharmacological processes such as antioxidant, anti-inflammatory, antithrombotic, apoptotic, and hepatoprotective effects. Antioxidative, antiproliferative, and antiangiogenic properties of curcumin have been noticed in recent years. However, the low solubility of curcumin and its severe degradation have made it impossible to introduce it in clinical use. In recent years, studies and reviews have been conducted to prepare and design polymeric micelles (PMMCs) on a nanoscale to improve the cellular transport of curcumin. Green tea flavonoids, including epicatechin, have recently received attention. In in vitro research, these compounds have been proposed as antioxidants by inhibiting lipid peroxidation, trapping free radicals, and chelating metal ions, and this property is mentioned due to their unique structure (therefore, the purpose of this study is to determine the effect The synergism of curcumin and epicatechin has been carried out in the investigation of apoptosis and cell proliferation of HT29 cell lines and apoptotic factors. Materials and methods: This study is experimental. After obtaining HT29 cells from the Pasteur Institute cell bank and completing cell passage and proliferation, the cells were distributed in triplicate wells across 7 test groups and 2 control groups (positive and negative). In test groups 1, 2, and 3, three concentrations of curcumin nanomicelles (10, 20, 50 µg/ml) were incubated in triplicate. In groups 4, 5, and 6, three concentrations of epicatechin (10, 20, 50 µg/ml) were incubated for 24 hours. Test group 7 consisted of HT29 cells treated with the IC50 concentration of nanomicelle curcumin combined with the IC50 concentration of epicatechin. Group 8, the positive control, consisted of cells treated with 5FU (100 µg/ml), while group 9, the negative control, consisted of cells exposed only to the cell culture medium. After the 24-hour incubation period, an MTT assay was performed to assess cell proliferation, and Annexin flow cytometry was used to determine the level of apoptosis. Results: In this study, epicatechin and curcumin have been able to decrease cell viability of colon cancer cells (HT29) and increase the percent of apoptotic cells P

Background and purpose: Today, despite the abundance of chemical drugs, the use of medicinal plants is increasing; Curcumin (curcumin) is a yellow pigment obtained from the turmeric plant and is considered the effective ingredient of turmeric. This crystalline and crystallized product is widely used in Indian medicine. Recently, the beneficial effects of curcumin on stomach, colon, and mouth cancers have been proven in mice. Curcumin usually plays its role through pharmacological processes such as antioxidant, anti-inflammatory, antithrombotic, apoptotic, and hepatoprotective effects. Antioxidative, antiproliferative, and antiangiogenic properties of curcumin have been noticed in recent years. However, the low solubility of curcumin and its severe degradation have made it impossible to introduce it in clinical use. In recent years, studies and reviews have been conducted to prepare and design polymeric micelles (PMMCs) on a nanoscale to improve the cellular transport of curcumin. Green tea flavonoids, including epicatechin, have recently received attention. In in vitro research, these compounds have been proposed as antioxidants by inhibiting lipid peroxidation, trapping free radicals, and chelating metal ions, and this property is mentioned due to their unique structure (therefore, the purpose of this study is to determine the effect The synergism of curcumin and epicatechin has been carried out in the investigation of apoptosis and cell proliferation of HT29 cell lines and apoptotic factors. Materials and methods: This study is experimental. After obtaining HT29 cells from the Pasteur Institute cell bank and completing cell passage and proliferation, the cells were distributed in triplicate wells across 7 test groups and 2 control groups (positive and negative). In test groups 1, 2, and 3, three concentrations of curcumin nanomicelles (10, 20, 50 µg/ml) were incubated in triplicate. In groups 4, 5, and 6, three concentrations of epicatechin (10, 20, 50 µg/ml) were incubated for 24 hours. Test group 7 consisted of HT29 cells treated with the IC50 concentration of nanomicelle curcumin combined with the IC50 concentration of epicatechin. Group 8, the positive control, consisted of cells treated with 5FU (100 µg/ml), while group 9, the negative control, consisted of cells exposed only to the cell culture medium. After the 24-hour incubation period, an MTT assay was performed to assess cell proliferation, and Annexin flow cytometry was used to determine the level of apoptosis. Results: In this study, epicatechin and curcumin have been able to decrease cell viability of colon cancer cells (HT29) and increase the percent of apoptotic cells P<0.05, which was in a dose-dependent manner, also the combination of these two drugs caused a synergistic effect in high dose P<0.05. Epicatechin in concentrations of 20, 10 μg/mL, 50, and 100 has a significant difference compared to the negative control group with P<0.05, which has caused a decrease in cell viability in colon cancer cells with increasing dose. Curcumin is the group Nanomicelle with epicatechin at IC50 concentration compared to the positive control group of 5-FU in HT-29 cell line has greatly reduced cell viability of HT-29 cell line showed that curcumin and epicatechin nano micelles had a synergistic effect. The results of cell apoptosis have shown that curcumin and epicatechin nano micelle groups at IC50 concentrations had a synergistic effect. Conclusion: epicatechin and curcumin have been able to increase the death rate of colon cancer cells (HT29) by increasing apoptosis, which indicates the anti-cancer effects of these compounds. So it can suggest these compounds in colon cancer therapeutics. [ABSTRACT FROM AUTHOR]

Purpose: Colorectal cancer (CRC) is one of the most common and fatal malignancies in humans, still leading to serious morbidity and mortality. We here aimed to investigate the effects of flavonoid apigenin, which is considered to have anti-tumoral activity on CRC with high epidemiological prevalence, on cell proliferation and cell survivals, and the positive and negative dose-dependent effects of genetic or mutational alterations in SWH pathway components on HT29 CRC cell lines. Methods: Human colon cancer cell lines HT-29 were commercially available. In each flask, 5 groups were formed, each of which consists of 5,000 cells for different dose groups and the cells were plated. After a 24 and 48 h incubation period, cytotoxicity values were measured by MTT assay and gene expression was assessed by real-time polymerase chain reaction (PCR) analysis method. Results: Application of 12.5 and 25 nM of apigenin significantly increased cell death in HT29 cell lines. LATS1, STK3 and TP53 gene expression decreased in the same dose groups compared to control and other groups. Conclusion: It has been concluded that TP53 gene is strongly correlated with LATS1 and STK3 genes among the SWH pathway factors in the progression of CRC and could be used as an important marker for early detection of malignant transmission. In addition, it may be effective in CRC cases especially when 25 nM of apigenin applies for therapeutic purpose. [ABSTRACT FROM AUTHOR]

Introduction: Niosome is a lipid carrier that can resolves some of the challenges facing the delivery of herbal medicines to tissues. The aim of the present study is to fabricate and evaluate the physiochemical properties of niosomal carriers containing Hedera helix extracts and evaluation of its toxicity to the HT29 cell line of colon cancer. Methods: Two niosomal formulations F0 (30% cholesterol and 70% tween60) and F1 (30% cholesterol and 70% spin60) containing extract of Hedera hilix were made using the thin film method. Then, according to the amount of drug loading, one of the formulations was selected. The pattern of drug release under normal and cancerous cell conditions, size and surface charge of the nanoparticles (using DLS) and the appearance of the nanoparticles (using SEM) of the selected formulation were investigated. Finally, the toxicity of the niosomal system containing extracts and free extracts on HT29 cell line was evaluated by MTT assay and niosomal system entry into HT29 cells was evaluated by system and cell staining. Results: Extract loading percentage, size and zeta potential for the selected formulation (F1) containing the extract were 95/43±2/43%, 132/5nm and -41/47±2/69mV, respectively. Release of the extract from the niosomal system is slow within 48 hours in normal and cancerous cell conditions. The appearance of the nanoparticles was smooth and spherical and extract niosomal had more toxicity to HT29 cell line colon cancer than free extract. Conclusion: The niosomal formulation of this study can be recommended for further research in colon cancer with respect to its physicochemical properties. [ABSTRACT FROM AUTHOR]

Introduction: Bifunctional radiosensitizer agents in which nitroaromatic moieties are attached through a linker to antineoplastic moieties have demonstrated higher cytotoxicity and radiosensitizer effects than the corresponding counterparts. This study was conducted to investigate the cytotoxicity and radiosensitizer activities of 2, 4-dinitrobenzene as a radiosensitizer moiety which connected to α, β unsaturated aryl ketones against the radioresistant human HT29 colon cancer cells. Methods: A series of bifunctional radiosensitizer derivatives that are composed of electron-affinic 2, 4-dinitrophenyl moiety and thiol reactive unsaturated conjugated ketones were prepared. The designed compounds were synthesized by the reaction of the corresponding 2, 4-dinitrobenzaldehyde, cyclohexanone and different aryl aldehydes. The cytotoxicity and radiosensitizer activity of the tested compounds were examined against HT29 colon cancer cells under aerobic condition. The IC50 value of the tested compounds and percent of survival cells were analyzed by the MTT assay. The clonogenic assay was used to assess the cell viability following treatment with the tested compounds with or without the combination of radiation. Results: This approach demonstrated that the tested compounds at the concentrations utilized have little or no cytotoxicity towards the radioresistant HT29 cell line but have great cytotoxicity and radiosensitizer activity when combined with irradiation. Conclusion: The novel bifunctional unsaturated conjugated aryl ketones which are thiol alkylators found to exhibit radiosensitivity activity. Consequently, these new developed compounds should be evaluated further to assess their potential efficacy with radiotherapy to combat malignancies in a pre-clinical animal model. [ABSTRACT FROM AUTHOR]

Aim of the study was to compare radiobiological effects of multiple vs. single low-dose pre-irradiation on the HT29 cell line. This regime is designed to be as similar as possible to fractionated tumour radiotherapy treatment, and to provide data on radiobiological effects on human tumour cells. Material and methods: The cell line used in the study was HT29 (human colorectal adenocarcinoma, American Type Culture Collection HTB-38™). Also, for comparison, the MRC5 cell line (human foetal lung fibroblasts, American Type Culture Collection CCL 171) was used. Four-day treatment in a 4 x 2 Gy regime was performed. Cell viability was evaluated by tetrazolium colorimetric MTT assay. Results: Multiple low-dose pre-irradiation induced a stronger radioadaptive response compared to single low-dose application in the HT29 cell line. Multiple pre-irradiation with 0.03 Gy and 0.05 Gy caused radioadaptive effects, while in both single and multiple low-dose pre-irradiation regimes 0.07 Gy led to radiosensitivity. Radiobiological effects induced in the HT29 cell line by low-dose pre-irradiation were evidently weak during the treatment time, because a single low-dose applied only on the first day gave no radioadaptive effects. In the MRC5 cell line different effects were registered, since radioadaptive response has not been observed after multiple or single pre-irradiation. Conclusions: The obtained data are interesting, especially for the possible application of low-dose pre-irradiation in radiotherapy. [ABSTRACT FROM AUTHOR]

Abstract: The aim of the present study was to reduce 5-FU side effects by targeted nanostructured lipid carriers (NLCs) to LDL receptors that are over expressed in colorectal carcinoma and also use of a new synthesized conjugate of retinoic acid as a cytotoxic agent. Fatty acyl amide derivative of retinoic acid was synthesized by its conjugation to octadecylamine with the expectation to improve its loading capacity in NLCs of 5-FU. The NLCs were prepared by an emulsification-solvent evaporation method using cholesterol and cholesteryl stearate. Physical properties and drug release were studied in NLCs. The cytotoxicity of NLCs loaded with 5-FU and retinoic acid conjugate was studied on colon cancer cells (HT29) using MTT assay. To confirm that drug targeting has been done through LDL receptors, APO-E was omitted from the cell culture and the MTT assay was repeated. FTIR and 1H NMR spectra confirmed successful production of the conjugate. Results showed the IC50 of free 5-FU was about 7.6 μM while in comparable concentration, the cytotoxicity of 5-FU loaded in NLCs containing the retinoic acid conjugate was nearly 2 fold of NLCs just loaded with 5-FU and more than 5 fold of free 5-FU. The retinoic acid conjugate loaded NLCs prepared by cholesterol can target LDL receptors of HT29 cells and seems promising in reducing 5-FU dose in colorectal cancer. [Copyright &y& Elsevier]

Apigenin (4',5,7-trihydroxyfiavone) is one of the leading components supporting targeted treatment options. We explored the cytotoxic and apoptotic effects of various doses of apigenin administered alone and together with 5-fluorouracil (5-FU)--a chemotherapeutic agent with high cytotoxicity--for different incubation periods, on morphologic, DNA, RNA (messenger RNA [mRNA]), and protein levels on the p53 mutant HT29 human colon adenocarcinoma cell line. Treatment with apigenin alone for a 72-hour incubation at 90-µM dose resulted in an apoptotic percentage of 24.92% (P = .001). A higher percentage (29.13%) was observed after treatment with the same dose of apigenin plus 5-FU for the same incubation period (P=.001). These results were confirmed as mRNA and protein expression levels of caspase-3 increased 2.567-fold and mRNA expression levels of caspase-8 increased 3.689-fold compared with the control group. On the other hand, mRNA expression levels of mammalian target of rapamycin (mTOR) and cyclin D1 (CCND1) decreased by 0.423-fold and 0.231-fold, respectively. To our knowledge this is the first study showing that treatment with apigenin alone results in cell cycle arrest through activation of caspase cascade and stimulation of apoptosis in HT29 cells. It also shows that use of apigenin plus 5-FU further increases this effect. This study draws attention to the probable clinical effectiveness of apigenin plus a chemotherapeutic agent with high cytotoxicity. It also highlights the induction of desirable apoptotic effects by targeting the caspase cascade pathway through administration of reduced doses for shorter incubation periods. [ABSTRACT FROM AUTHOR]

Fruits and vegetables are a good source of potentially biologically active compounds. Their regular consumption in the human diet can help reduce the risk of developing chronic diseases such as cardiovascular diseases and cancer. Plants produce additional chemical substances when subject to abiotic stress or infected by microorganisms. The phytochemical profile of spinach leaves (Spinacia oleracea L.), which is a vegetable with widely recognized health-promoting activity, has been affected by applying root hypoxic and re-oxygenation stress during plant growth. Leaf juice at different sampling times has been subject to liquid chromatography mass spectrometry (LC-MSn) analysis and tested on the human colorectal adenocarcinoma cell line HT29 by using the Comet assay. The cells were previously treated with H2O2 to simulate the presence of an oxidative stress (as in colon cancer condition) and the leaf juice application resulted in a significant antioxidant and protective in vitro effect. The duration of the hypoxic/re-oxygenation stress imposed on the plant reflects the antioxidant leaf juice content. After hypoxic stress (24 h) and reoxygenation (2 h), we show a decrease (50%) of the relative abundance of the principal identified antioxidant molecules but a higher antioxidant activity of the spinach juice on HT29 cells (20%). Data shows a complex relation between plant growing conditions and the modulation of secondary metabolites content in leaf juice that results in different chemo-protective activities in colon cancer cells. [ABSTRACT FROM AUTHOR]