ABSTRACT
BACKGROUND: In women, breast cancer is the second most frequent type of cancer. Looking for new and effective cancer-specific therapies with little to no adverse effects on healthy cells is critical. OBJECTIVE: Minocycline, a second-generation tetracycline, has shown anticancer effects by targeting multiple pathways in various cancers. This study aimed to determine minocycline effects on the cell proliferation, apoptosis, and invasion of the human MCF-7 cells. METHODS: MTT assay was used to evaluate the cytotoxicity of minocycline on the cells. Flow cytometry was performed to investigate the induction of apoptosis and the cell cycle progression. The expression levels of apoptotic and migration proteins and genes were assessed by western blotting and qRT-PCR. The scratch test was performed to evaluate the anti-migration effect of the drug. RESULTS: The results indicated that the IC50 value of minocycline for MCF-7 cells was 36.10 µM. Minocycline treatment caused sub-G1 cell accumulation, indicating a significant apoptotic effect on the MCF-7 cells. Annexin-V/PI staining revealed a significant rise in early and late apoptotic cell percentages. Minocycline up-regulated Bax and Caspase-3 expression and down-regulated Bcl-2 and Pro-Cas3. The scratch test revealed significant anti-migration effects for minocycline. Furthermore, it caused down-regulation of MMP-2 and MMP-9 in a concentration-dependent method. CONCLUSION: These findings further confirmed the anticancer effect of minocycline and highlighted that minocycline maybe considered as potential therapeutic agent for breast cancer treatment.
Subject(s)
Breast Neoplasms , Minocycline , Female , Humans , MCF-7 Cells , Minocycline/pharmacology , Minocycline/therapeutic use , Breast Neoplasms/genetics , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 2/metabolism , Apoptosis , Cell Proliferation , Cell Line, TumorABSTRACT
This research work explains the development of an electrochemical immunosensor for the selective recognition of SNCA in human biofluids. An innovative protocol was proposed for the green synthesis of gold nanoparticle-supported dimethylglyoxime (AuNPs@DMGO) using one-step electrogeneration method. Also, the application of AuNPs@DMGO for the sensitive quantification of α-Synuclein (SNCA) protein and its biomedical analysis. So, an innovative sandwich immunosensor was designed for the sensitive identification of SNCA antigen in an aqueous solution. The gold nanoparticles (AuNPs) were decorated on the surface of the glassy carbon electrode by chronoamperometry technique to provide appropriate immobilization surface with a large number of active sites for immobilization of specific biotinylated antibody (Ab1) and against SNCA protein. Then, the sandwich-type immuno-platform was completed by the attachment of secondary antibody (HRP conjugated Ab [Ab2]) to the primary complexes on the surface of the electrode. For the first time, α-Synuclein protein was measured with an acceptable linear range of 4-64 ng/mL and a lower limit of quantification of 4 ng/mL. Benefiting from the simplicity and high sensitivity, the proposed method shows a potential of employment in clinical applications and high-throughput screening of Parkinson's disease using POC.
Subject(s)
Biosensing Techniques , Metal Nanoparticles , Parkinson Disease , Humans , Gold/chemistry , Biosensing Techniques/methods , alpha-Synuclein , Metal Nanoparticles/chemistry , Parkinson Disease/diagnosis , Limit of Detection , Immunoassay/methods , Antibodies/chemistry , Electrochemical Techniques/methodsABSTRACT
Heat stress increases the core body temperature through the pathogenic process. The pathogenic process leads to the release of free radicals, such as superoxide production. Heat stress in the central nervous system (CNS) can cause neuronal damage and symptoms such as delirium, coma, and convulsion. TRPV1 (Transient Receptor Potential Vanilloid1) and TRPV4 genes are members of the TRPV family, including integral membrane proteins that act as calcium-permeable channels. These channels act as thermosensors and have essential roles in the cellular regulation of heat responses. The objective of this study is to examine the effect of general heat stress on the expression of TRPV1 and TRPV4 channels. Furthermore, oxidative markers were measured in the brain of the same heat-stressed mice. Our results show that heat stress leads to a significant upregulation of TRPV1 expression within 21-42 days, while TRPV4 expression decreased significantly in a time-dependent manner. Alterations in the oxidative markers were also observed in the heat-stressed mice.
Subject(s)
Brain/metabolism , Hyperthermia, Induced , Oxidative Stress/physiology , TRPV Cation Channels/metabolism , Animals , Brain/pathology , Calcium Channels/metabolism , Hyperthermia, Induced/methods , Male , Mice, Inbred C57BLABSTRACT
INTRODUCTION: Curcumin is a polyphenolic natural compound, which has demonstrated to possess antioxidant, anti-inflammatory, and anticancer effects in vitro & in vivo. However, its applicability in cancer therapy has been limited due to its poor cellular uptake. Here, we aimed to evaluate the anticancer effect of novel gemini curcumin (Gemini-Cur) on the gastric cancer AGS cells. METHOD: The AGS cancerous and HFF-2 non-cancerous cells were treated with Gemini-Cur and curcumin (Cur) in a time- and dose-dependent manner. Cellular toxicity was studied using MTT, fluorescence microscopy, annexin V/FITC, and cell cycle assays. Additionally, real-time PCR and western blotting were employed to evaluate the expression of Bax, Bcl-2 and survivin genes. RESULTS: Our data indicated that Gemini-Cur is significantly taken into AGS cells compared to Cur. Moreover, the viability of Gemini-Cur treated cells was significantly reduced in a time- and dose-dependent manner (p < 0.001). Gemini-Cur compound induced G2/M cell cycle arrest that was followed by apoptosis in a time-dependent manner (p < 0.0001). DISCUSSION: Taken together, our findings support the idea that Gemini-Cur has the potential to be considered as an anticancer agent.
Subject(s)
Apoptosis/drug effects , Cell Proliferation/drug effects , Curcumin , Stomach Neoplasms , Cell Line, Tumor , Cell Survival/drug effects , Curcumin/pharmacokinetics , Curcumin/pharmacology , Humans , Stomach Neoplasms/drug therapy , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathologyABSTRACT
Thiosemicarbazones (TSCs) and their metal complexes exhibit pronounced and selective cytotoxic potential against a broad span of cancers. Here, we assessed the anti-cancer activity of a water-soluble copper(II) complex of thiosemicarbazone (Cu-TSC) against two cancer cell lines of human leukemia. Our analysis revealed that Cu-TSC treatment results in a time and dose-dependent growth inhibition in K562 and KG1a cells while sparing normal human fibroblast (HFF2) cells. The IC50 values for the Cu-TSC treatment were measured to be 21.7 ± 1.5 µM and 50.25 ± 2.5 µM for K562 and KG1a cells, respectively. Cell cycle analysis indicated that Cu-TSC induces the accumulation of cells in the sub-G1 fraction as well as the reversible arrest in G0/G1 and G2/M phases in K562 and KG1a cells, respectively. Furthermore, the occurrence of apoptosis as the prime mode of cell death was verified through apoptotic body formation, phosphatidylserine externalization, and caspase-3 activation. Additionally, the real-time quantitative PCR analysis revealed that Cu-TSC triggers apoptosis in both cell lines via the upregulation of caspases-8, -9, and the changing of Bax/Bcl2 ratio. Finally, flow cytometric analysis confirmed that Cu-TSC treatment causes the enhancement of reactive oxygen species formation in both K562 and KG1a cells. Altogether, these findings suggest that Cu-TSC is a promising inducer of apoptosis in leukemia cells and carries potential as an anti-cancer compound.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Organometallic Compounds/pharmacology , Thiosemicarbazones/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Cycle/drug effects , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Organometallic Compounds/chemical synthesis , Organometallic Compounds/chemistry , Reactive Oxygen Species/metabolism , Solubility , Thiosemicarbazones/chemical synthesis , Thiosemicarbazones/chemistry , Tumor Cells, Cultured , Water/chemistryABSTRACT
MicroRNAs, a class of gene expression regulatory non-coding RNAs, participate in the pathogenic mechanisms of gastric cancer which is one of the life-treating cancers. Due to its aberrant expression in some types of human cancer, miR-383 has the value of being investigated in relation to cancer treatment and diagnosis. MiR-383 is placed in intron of SGCZ, a protein-coding gene, which is subject to dysregulation in various diseases. The purpose of the current study was to investigate the contribution of miR-383 to intestinal-type gastric adenocarcinoma tumorigenesis. The expression level of miR-383 was investigated by qRT-PCR in pairs of tumorous and adjacent tumor-free tissues of 40 patients with gastric cancer during endoscopy. Also, the susceptibility of miR-383 as a tumor marker and the relationship between its aberrant expression and clinicopathological features were determined. qRT-PCR data showed that miR-383 was dysregulated during gastric tumorigenesis. MiR-383 was dramatically downregulated up to sevenfold in intestinal-type gastric adenocarcinoma compared with adjacent tumor-free tissues (P < 0.001). Misregulation of miR-383 did not reveal a significant correlation with clinical characteristics. The ROC area of 80% with 76% sensitivity and 84% specificity was determined by P < 0.001. The current study demonstrated downregulation of miR-383 in intestinal-type gastric adenocarcinoma. Downregulation of miR-383 might be used as a potential tumor marker for the diagnosis of gastric cancer or could be a potential target for gene therapy.
Subject(s)
Adenocarcinoma/pathology , Biomarkers, Tumor/genetics , Intestinal Neoplasms/pathology , Introns/genetics , MicroRNAs/genetics , Stomach Neoplasms/pathology , Adenocarcinoma/genetics , Case-Control Studies , Female , Gene Expression Regulation, Neoplastic , Humans , Intestinal Neoplasms/genetics , Male , Middle Aged , Neoplasm Grading , Prognosis , Stomach Neoplasms/geneticsABSTRACT
BACKGROUND: Stanniocalcin-1 (STC1) and nuclear factor (NF)-κB subunit p65 transcription factor are involved in various types of human malignancies. The roles of STC1 and NFκB-p65 in colorectal cancer (CRC) are still not fully understood. We investigated expression levels of NF-κB p65 and STC1 and also correlations between STC1 and NF-κB p65 expression and clinicopathological features in CRC. METHODS: Tumor tissue samples were collected from 48 patients with CRC. RT-PCR and Real-time PCR analysis was performed to examine mRNA levels of STC1 and NF-κB p65. RESULTS: The relative mRNA levels of STC1 and NF-κB p65 were significantly higher in tumor tissues than in adjacent mucosa (p = 0.025 and p = 0.044, respectively). The data also showed that STC1 and NF-κB p65 mRNA levels were not significantly associated with clinicopathological characteristics. In addition, there was no association between expression levels of STC1 and NF-κB p65 in tumor samples. CONCLUSIONS: Our data indicate that STC1 and NF-κBp65 is activated constitutively in colorectal carcinoma tissues, suggesting that activation of these factors might play an important role in colorectal tumorigenesis. Future studies should examine STC1 and NF-κBp65 as a molecular target for the treatment of CRC.
Subject(s)
Colorectal Neoplasms/metabolism , Glycoproteins/genetics , Transcription Factor RelA/genetics , Adult , Aged , Colorectal Neoplasms/etiology , Colorectal Neoplasms/pathology , Female , Humans , Male , Middle Aged , RNA, Messenger/analysisABSTRACT
Aldehyde oxidase (AO), an important enzyme in the biotransformation of drugs and xenobiotics, is inhibited by flavonoids. This enzyme can metabolize both aldehydes and N-heterocycles. In this work, a set of 15 flavonoids was assessed for inhibitory activity on the AO oxidation of vanillin as an aldehyde substrate. Spectrophotometrically determined IC50 values showed that myricetin, quercetin, and epicatechin were the most potent inhibitors. The results also revealed that the inhibition of vanillin oxidation by flavonoids was stronger than that of phenanthridine oxidation (an N-heterocyclic substrate) as reported previously. In order to investigate the important structural features responsible for the inhibitory effects of the studied flavonoids, a quantitative structure-activity relationship (QSAR) analysis was performed. This study showed that the size of the flavonoids was the most important factor inversely affecting their potencies. The QSAR model can be used more broadly to predict the AO inhibitory activity of flavonoid-like structures for application in food-drug and drug-drug interaction studies.
Subject(s)
Aldehyde Oxidase/antagonists & inhibitors , Computer-Aided Design , Drug Design , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Flavonoids/chemistry , Flavonoids/pharmacology , Liver/drug effects , Molecular Dynamics Simulation , Aldehyde Oxidase/chemistry , Aldehyde Oxidase/metabolism , Animals , Liver/enzymology , Male , Molecular Structure , Protein Conformation , Quantitative Structure-Activity Relationship , Rats, Sprague-DawleyABSTRACT
Colon cancer is a significant global health issue, and its primary treatment, chemotherapy, is limited by toxicity and drug resistance. This has led researchers to explore alternative therapeutic approaches. One such approach is the use of chitosan, a natural biopolymer with anti-cancer properties, and paclitaxel, a potent chemotherapeutic agent with promising activity against many types of cancer. In this study, the effectiveness of a chitosan hydrogel that contains a complex of gold nanoparticles with paclitaxel in treating LS174T colon cancer cell line was investigated. The synthesized chitosan hydrogel was characterized and used to treat the colon cancer cells in cell culture. MTT assay and apoptotic gene expression analysis were conducted to evaluate the complex's effectiveness. The results showed that the chitosan hydrogel-loaded gold nanoparticle-paclitaxel complex exhibited a potent cytotoxic effect against the cancer cells. Moreover, the treatment resulted in a significant increase in pro-apoptotic BAX and BAD expression and a decrease in anti-apoptotic BCL2 expression, indicating a pro-apoptotic effect. These findings suggest that utilizing a chitosan hydrogel that contains a complex of gold nanoparticles with paclitaxel shows promise as a viable treatment option for colon cancer. Further research is needed to determine the potential efficacy and safety of this treatment approach in clinical settings.
Subject(s)
Chitosan , Colonic Neoplasms , Metal Nanoparticles , Nanoparticles , Humans , Gold , Hydrogels , Cell Line, Tumor , Paclitaxel/pharmacology , Colonic Neoplasms/drug therapyABSTRACT
BACKGROUND: Gemini Curcumin (Gemini-Cur) is the latest nanoformulation of curcumin with a significant apoptotic effect on cancer cell lines. OBJECTIVE: This in vitro study aims to evaluate the apoptotic effects of Gemini-Cur toward MDA-MB-468 breast cancer cell lines and further the related mechanism of apoptosis. METHODS: The cytotoxicity of Gemini-Cur toward MDA-MB-468 cell lines was tested using MTT assay. Furthermore, the expression ratio of Bax/Bcl-2 was evaluated by qRT-PCR. Consequently, the protein expression of Bax/Bcl-2, survivin, and caspase-3 was measured using western blotting. RESULTS: Having treated MDA-MB-468 cell lines with Gemini-Cur, the IC50 values were found to be 44.44 and 31.63 µM at 24 and 48 h, respectively. Our findings showed that Gemini-Cur significantly suppresses cancer cell proliferation in a time- and dose-dependent manner. Furthermore, the data revealed that curcumin nanoformulation induces apoptosis in MDA-MB-468 cells through modulation of the expression of Bax, Bcl-2, Survivin, and Caspase-3. CONCLUSION: The data of the current study propose that Gemini-Cur can be considered a promising candidate against triple-negative breast cancer.
Subject(s)
Breast Neoplasms , Curcumin , Triple Negative Breast Neoplasms , Apoptosis , Breast Neoplasms/drug therapy , Caspase 3/genetics , Caspase 3/metabolism , Cell Line, Tumor , Cell Proliferation , Curcumin/pharmacology , Female , Humans , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Survivin , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolismABSTRACT
Hemophilia A is an X-linked congenital bleeding disorder caused by Factor VIII deficiency. Different mutations including point mutations, deletions, insertions and inversions have been reported in the FVIII gene, which cause hemophilia A. In the current study, with the use of conformational sensitive gel electrophoresis (CSGE) analysis, we report a novel 1-nt deletion in the A6 sequence at codons 1328-1330 (4040-4045 nt delA) occurring in exon 14 of the FVIII gene in a seven-year-old Iranian boy with severe hemophilia A. This mutation that causes frameshift and premature stop-codon at 1331 has not previously been reported in the F8 Hemophilia A Mutation, Structure, Test and Resource Site (HAMSTeRS) database.
ABSTRACT
BACKGROUND: Despite recent advances in therapy, colorectal cancer remains a leading cause of death in affected people. Curcumin is the main bioactive compound of turmeric that has been demonstrated as an effective agent against cancer. However, its poor stability and bioavailability limit therapeutic application. We previously showed that delivery of curcumin by using gemini surfactant nanoparticles called gemini curcumin (Gemini-Cur) could improve its solubility, uptake and toxic effect on breast and ovarian cancer cells. Here, we aimed to investigate the anticancer activity of Gemini-Cur in both p53-mutant and p53-wild type colorectal cancer cells. The toxicity of Gemini-Cur on HT-29 and HCT116 was studied through MTT, uptake kinetics, fluorescence microscopy, annexin V/FITC, and cell cycle assays. Also, real-time PCR and western blotting were performed to evaluate the expression of p53, p21, BAX, BCL-2, and NOXA genes. Our data showed that Gemini-Cur not only enters cells quite rapidly compared to free curcumin crystals, but also suppresses HT-29 and HCT-116 cells proliferation in a time- and dose-dependent manner (p < 0.001). The IC50 values as well as apoptosis assays showed that p53-wild type cells are sensitive to Gemini-Cur. Flow cytometry also revealed that the number of apoptotic cells is dramatically increased in HCT-116 cells earlier than HT-29 cells (p < 0.0001). Gemini-Cur upregulated apoptotic genes including p53 (in both mutant and wild-type forms), p21, NOXA and BAX while decreased anti-apoptotic BCL-2 in mRNA and protein level (p < 0.0001). As a hallmark of apoptosis, the expression ratio of BAX/BCL-2 was significantly increased in all treated cells. Taken together, our findings demonstrated that Gemini-Cur suppresses the proliferation of cancer cells via induction of apoptosis and could be considered as novel nano-formulated phytochemical for cancer targeting.
Subject(s)
Antineoplastic Agents , Colorectal Neoplasms , Curcumin , Antineoplastic Agents/pharmacology , Apoptosis , Cell Line, Tumor , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Curcumin/pharmacology , HCT116 Cells , Humans , Tumor Suppressor Protein p53/geneticsABSTRACT
Quartz crystal nanobalance (QCN) sensors are considered as powerful mass sensitive sensors to determine materials in the sub-nanogram level. In the first part of this study, a single piezoelectric QCN modified with polypyrrole (PPy) has been tested for detection and determination of nickel ions in the solution at room temperature. The developed method was successfully applied for detection of total nickel in samples taken from several hot springs located at the Northwest of Iran. The frequency shifts were linear with respect to the concentration of nickel in solution. Using this method, nickel can be measured in the range of 3-20 mg L(-1). A lower limit of detection of 0.79 mg L(-1) and a sensitivity factor of 4.429 Hz/mg L(-1) were obtained. Some possible interference such as heavy metal ions (lead, mercury, and cadmium) was checked. No major interference was observed with the performance of the sensor except for mercury. To evaluate the ability of the PPy-modified QCN in discriminating between nickel ions and interfering mercury ions, a principal component analysis (PCA) was carried out. PCA was utilized to process the frequency response data of the single piezoelectric crystal at different times, considering different adsorption-desorption dynamics of nickel and interfering mercury ions on electrode. Using PCA, it was found that about 97.90% of the data variance could still be explained by two principal components (PC1 and PC2). The score plot of the data for the first two PCs showed that the PPy-modified QCN yields favorable identification and quantification performances for nickel ions. The accuracy of method for hot spring samples was evaluated and RSD of 4.10% was obtained.
Subject(s)
Nickel/chemistry , Principal Component Analysis , Quartz/chemistry , Solutions/chemistryABSTRACT
BACKGROUND: Despite the advances in screening during the past decades, colorectal cancer (CRC) still is a leading cause of cancer deaths worldwide. Therefore, the development of new diagnostic methods is necessary. AIM: The aim of this study was to compare methylation changes of SRY-Box 21 (SOX21) gene promoter in tumor tissues and their normal adjacent mucosa in patients with CRC and to examine the relationship between the methylation levels and demographic/clinicopathological factors. MATERIALS AND METHODS: A total of 41 CRC patients participated in the present study. After the extraction of DNA and bisulfite treatment of the samples, the methylation levels were determined by using the MethyLight method. STATISTICAL ANALYSIS: Two-sided Mann-Whitney U test was used to compare the median level of methylation in tumor tissues and their adjacent normal mucosa. RESULTS: The methylation rates in tumor tissue samples were significantly higher compared to their adjacent normal mucosa (P < 0.0001). No association between demographic/clinicopathological factors and methylation status observed in tumor tissues. A receiver operating characteristics curve was constructed and tissue samples exhibited a sensitivity of 80.5% and specificity of 97.6% for SOX21 promoter methylation. CONCLUSION: The results of this study indicated the high potential of SOX21 gene promoter methylation as a candidate noninvasive diagnostic biomarker in stool and plasma of colorectal cancer patients. However, further studies with larger sample sizes are required to evaluate the specific role of SOX21 methylation as a biomarker for early detection of CRC.
Subject(s)
Colorectal Neoplasms/genetics , DNA Methylation , SOXB1 Transcription Factors/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Early Detection of Cancer , Epigenesis, Genetic , Female , Humans , Male , Middle Aged , SOXB1 Transcription Factors/metabolismABSTRACT
There are several polymerase chain reaction (PCR)-based approaches for the analysis of known mutations. The PCR-amplification refractory mutation system (PCR-ARMS) is one of the best known and frequently used for the detection of beta-thalassemia (beta-thal) mutations. However, there is an important point to be considered when searching for the frameshift codon (FSC) 8 (-AA) and FSC 8/9 (+G) mutations. Whereas the primer is specific for the FSC 8 mutation only, the primer for the FSC 8/9 mutation does not discriminate between the FSC 8/9 and FSC 8 mutations. Thus, the high number of FSC8/9 mutations reported in countries like India, Pakistan and some regions of Iran may be due to the use of the FSC 8/9 primer, without taking the FSC 8 mutation into account. It is thus advisable to test for FSC 8 before the FSC 8/9 mutation whenever PCR-ARMS is the method of investigation for these two mutations.
Subject(s)
Codon/genetics , Frameshift Mutation , Polymerase Chain Reaction/methods , beta-Thalassemia/genetics , DNA Primers/genetics , Humans , Polymerase Chain Reaction/standards , Reproducibility of Results , Sensitivity and Specificity , beta-Thalassemia/diagnosisABSTRACT
Damage to the reward brain system is regarded as a key consequence of narcotic drug abuse, including methamphetamine (METH). The Prefrontal cortex (PFC) is one of the brain areas associated with mesocortical pathway, which plays principal roles in cognitive behavior and memory function. In spite of the potential role of PFC in METH abuse, little is known about METH-induced neurotoxicity in PFC region. In this study, we examined neurotoxicity-associated molecular pathways such as inflammation, apoptosis and autophagy in PFC under the influence of METH using quantitative real time PCR (qPCR). Besides, the protein levels of brain derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) as markers of synaptic plasticity and gliosis were inspected, respectively. Then we performed stereological analysis in METH-treated rats. Based on our findings, qPCR analysis revealed impaired autophagy, increased apoptosis and inflammation along with histological alterations in PFC, augmented astrogliosis as well as a significant reduction in the level of BDNF. Collectively, our molecular and histological data imply that METH administration in PFC region provoked differential expression changes in neurotoxicity-associated signaling cascades namely inflammation, apoptosis and autophagy coupled with significant PFC atrophy.
Subject(s)
Apoptosis/drug effects , Autophagy/drug effects , Central Nervous System Stimulants/pharmacology , Methamphetamine/pharmacology , Neurons/drug effects , Prefrontal Cortex/drug effects , Animals , Brain-Derived Neurotrophic Factor/metabolism , Glial Fibrillary Acidic Protein/metabolism , Inflammation/metabolism , Male , Neurons/metabolism , Prefrontal Cortex/metabolism , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Curcumin, the polyphenolic constituent of turmeric, has been recognized as an effective anticancer agent in the treatment of breast cancer. However, the poor bioavailability of curcumin triggers finding of new approaches for elevating its therapeutic efficiency. PURPOSE: We aimed to use gemini surfactant nanocarriers for curcumin in order to overcome its limitations. STUDY DESIGN: We investigated the in vitro characterization of gemini surfactant-curcumin (Gemini-Cur) and examined its antiproliferative & apoptotic activities on breast cancer cell lines. METHODS: Gemini-Cur polymersomes were synthesized through nanoprecipitation method and characterized by dynamic light scattering (DLS), transmission and scanning electron microscopies, HPLC and X-ray diffraction (XRD). The anticancer effect of Gemini-Cur nanoparticles was studied on three different breast cancer cell lines including MCF-7, SkBr-3 and MDA-MB-231 through uptake kinetics, viability & cytotoxicity recordings and apoptotic assays. Furthermore, qRT-PCR was performed to evaluate the expression of apoptotic genes including p16INK4a, p14ARF, Bax and Bcl-2. RESULTS: According to physicochemical analysis, the average particle size, zeta potential value and drug entrapment efficiency for Gemini-Cur compound were recorded as 161⯱â¯6.2â¯nm, +5.32â¯mV and 89.13%⯱â¯0.93, respectively. XRD analysis also confirmed the incorporation of curcumin in gemini surfactant micelles. Regarding the enhanced cellular uptake of sphere shaped Gemini-Cur, our data showed that this nano compound suppresses cancer cell proliferation via induction of apoptosis. Moreover, qRT-PCR analysis revealed that Gemini-Cur could effectively upregulate the expression of p16INK4a, p14ARF and Bax, while significantly decreasing the Bcl-2 expression in these breast cancer cells. CONCLUSION: Our data demonstrates the great potential of gemini surfactants for efficient delivery of curcumin and subsequently, the improvement of its anticancer effect. Therefore, it is sagacious to support the idea that Gemini-Cur nano compound might have the potential to be considered as an anticancer agent.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Breast Neoplasms/drug therapy , Curcumin/pharmacology , Nanoparticles/chemistry , Surface-Active Agents/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Apoptosis/drug effects , Apoptosis/genetics , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Curcumin/chemistry , Drug Screening Assays, Antitumor , Dynamic Light Scattering , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Micelles , Particle Size , X-Ray DiffractionABSTRACT
BACKGROUND: MicroRNAs (miRNAs) are effective regulators of gene expression that play a pivotal role in the pathogenesis of colorectal cancer (CRC) and various other cancers. The high prevalence of aberrant miRNA expression in CRC suggests that they can be used as biomarkers and anticancer molecules for therapeutic purposes. There is evidence that microRNA-299-5p (miR-299-5p) is associated with vital cell processes (e.g. epithelial-mesenchymal transition, proliferation, and tumorigenicity) and its improper expression with tumorigenesis in many types of human cancer. This prospective study investigated the contribution of miR-299-5p to CRC tumorigenesis. METHODS: The real-time reverse transcription-polymerase chain reaction was used to examine miR-299-5p expression levels prospectively in 40 sample pairs of CRC tissue and adjacent noncancerous tissue (>2 cm from cancer tissue). The ability of miR-299-5p to function as a tumor marker was also examined. RESULTS: The expression levels of miR-299-5p were significantly downregulated in the group of CRC samples compared with matched noncancerous tissue samples. No significant relationship was found between miR-299-5p expression levels and clinicopathological features. Receiver operating characteristic analysis gave an area under the curve of 71% for miR-299-5p with 68% sensitivity and 78% specificity (P=0.001). CONCLUSION: The miRNA miR-299-5p may be considered as a tumor marker in CRC and could be of assistance as a potential predictive biomarker in the diagnosis of this cancer.
ABSTRACT
BACKGROUND: Long non-coding RNAs (lncRNAs), a class of regulatory RNAs, play a major role in various cellular processes. Long intergenic non-coding RNAs (lincRNAs), a subclass of lncRNAs, are involved in the trans- and cis-regulation of gene expression. In the case of cis-regulation, by recruiting chromatin-modifying complexes, lincRNAs influence adjacent gene expression. METHODS: We used quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) to evaluate the coexpression of LOC100287225, a lincRNA, and DCC, one of its adjacent genes that is often decreased in colorectal cancer, in pairs of tumor and adjacent tumor-free tissues of 30 colorectal cancer patients. RESULTS: The qRT-PCR results revealed the misregulation of these genes during tumorigenesis. Their relative expression levels were significantly lower in tumor tissues than adjacent tumor-free tissues. However, the analysis found no significant correlation between reduced expression of these genes. CONCLUSIONS: Our study demonstrated the concurrent misregulation of DCC and LOC100287225 in colorectal cancer.
Subject(s)
Gene Expression Regulation, Neoplastic , RNA, Long Noncoding/genetics , Receptors, Cell Surface/genetics , Tumor Suppressor Proteins/genetics , DCC Receptor , Female , Humans , Male , Middle Aged , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
INTRODUCTION: MicroRNAs are non-coding RNAs that regulate the gene expression at post-transcriptional level. This futuristic study characterized the contribution of miR-1287 to the colorectal cancer (CRC) tumorigenesis. METHODS: The real-time reverse transcription-polymerase chain reaction was used to examine miR-1287 expression levels, prospectively in 40 pairs of CRC tissue samples and adjacent noncancerous tissues (>2 cm from cancer tissue). RESULTS: No significant relationship was found between miR-1287 expression levels and clinicopathological features. Showing significant changes overall, MiR-1287 was significantly upregulated in the group of CRC samples compared with matched noncancerous tissue samples. A receiver operating characteristic (ROC) curve also showed ROC area (AROC) of 34 % with 1.0 and 0.02 sensitivity and specificity, respectively. Expression of miR-1287, with a value of 0.34, P value = 1.98, and P > 0.05, revealed that this microRNA has a low sensitivity and specificity to be regarded as a tumor marker. CONCLUSIONS: With regard to recent increased rate of CRC in the world, the present study may be a contribution, though very small, in the diagnosis and consequently in the treatment of CRC patients.