Anti-metastatic Property Research Articles

Phytochemical composition of the diethyl ether extract of Artemisia lactiflora Wall. ex DC and its antimetastatic activity in human lung cancer cells

Artemisia lactiflora Wall. ex DC. is a traditional Chinese medicinal plant used in the treatment of menstrual and hepatic disorders due to its antioxidant and anti-inflammatory properties. However, its anti-metastatic activity, which is the clinical challenge of lung cancer treatment, has not yet been reported. From the diethyl ether extract of Artemisia lactiflora, the four terpenoids, including dihydroactinidiolide, megastigmatrienone, alpha-curcumene, and dehydrovomifoliol, were the most intense peaks observed using LC-MS/MS, whereas bis (2-ethylhexyl) phthalate was a contaminant. In a transwell assay, the A. lactiflora diethyl ether extract (32 μg/ml) and dihydroactinidiolide (250 μg/ml) markedly inhibited the migration and invasion of non-small cell lung cancer (NSCLC) cells, similar to the standard anti-metastatic drug (capmatinib). Western blot analysis revealed that mesenchymal N-cadherin is downregulated in NSCLC cells under the treatment conditions. The potential anti-metastatic property of dihydroactinidiolide is promising as a new candidate anti-metastatic agent for lung cancer treatment.

Morin inhibits osteosarcoma migration and invasion by suppressing urokinase plasminogen activator through a signal transducer and an activator of transcription 3.

Osteosarcoma, the most common primary bone cancer that affects adolescents worldwide, has the early metastatic potential to be responsible for high mortality rates. Morin has a multipurpose role in numerous cancers, whereas little is known about its role in osteosarcoma migration and invasion. Therefore, we hypothesized that morin suppresses the invasive activities and the migratory potential of human osteosarcoma cells. Our results showed that morin reduced migration and invasion capabilities in human osteosarcoma U2OS and HOS cells. Moreover, morin inhibited the urokinase plasminogen activator (uPA) expression through a signal transducer and an activator of transcription-3 (STAT3) phosphorylation. After STAT3 overexpression, the decrease of the migratory potential and uPA expression caused by 100 μM of morin in U2OS cells was countered, indicating that STAT3 contributes to the antimetastatic property of morin in human osteosarcoma cells by reducing uPA. In conclusion, morin may be a potential candidate for the antimetastatic treatment of human osteosarcoma.

Dichloro Ru(II)-p-cymene-1,3,5-triaza-7-phosphaadamantane (RAPTA-C): A Case Study.

The use of organometallic compounds to treat various phenotypes of cancer has attracted increased interest in recent decades. Organometallic compounds, which are transitional between conventional inorganic and organic materials, have outstanding and one-of-a-kind features that offer fresh insight into the development of inorganic medicinal chemistry. The therapeutic potential of ruthenium(II)-arene RAPTA-type compounds is being thoroughly investigated, specifically owing to the excellent antimetastatic property of the initial candidate RAPTA-C. This review gives a thorough analysis of this complex and its evolution as a potential anticancer drug candidate. The numerous mechanistic investigations of RAPTA-C are discussed, and they are connected to the macroscopic biological characteristics that have been found. The "multitargeted" complex described here target enzymes, peptides, and intracellular proteins in addition to DNA that allow it to specifically target cancer cells. Understanding these may allow researchers to find specific targets and tune a new-generation organometallic complex accordingly.

Perturbation Analysis of a Prognostic DDX3X-Mediated Gene Expression Signature Identifies the Antimetastatic Potential of Chaetocin in Hepatocellular Carcinoma

ATP-dependent RNA helicase DDX3X, also known as DEAD (Asp-Glu-Ala-Asp) Box Polypeptide 3, X-Linked (DDX3X), is critical for RNA metabolism, and emerging evidence implicates ATP-dependent RNA helicase DDX3X’s participation in various cellular processes to modulate cancer progression. In this study, the clinical significance of DDX3X was addressed, and DDX3X was identified as a biomarker for poor prognosis. An exploration of transcriptomic data from 373 liver cancer patients from The Cancer Genome Atlas (TCGA) using Ingenuity Pathway Analysis (IPA) suggested an association between DDX3X expression and cancer metastasis. Lentiviral-based silencing of DDX3X in a hepatocellular carcinoma (HCC) cell line resulted in the suppression of cell migration and invasion. The molecular mechanism regarding ATP-dependent RNA helicase DDX3X in liver cancer progression had been addressed in many studies. I focused on the biological application of the DDX3X-mediated gene expression signature in cancer therapeutics. An investigation of the DDX3X-correlated expression signature via the L1000 platform of Connectivity Map (BROAD Institute) first identified a histone methyltransferase inhibitor, chaetocin, as a novel compound for alleviating metastasis in HCC. In this study, the prognostic value of DDX3X and the antimetastatic property of chaetocin are presented to shed light on the development of anti-liver cancer strategies.

Antitumor activity of the novel pyridine derivative

Introduction: The study aim was to explore a toxicological property and antitumor action of the novel pyridine deriv­ative LHT-17-19 in cell culture and on experimental models of lung cancer in mice.
 Materials and methods: The study was performed on male and female ICR(CD-1), male BALB/c, male BALB/c nu/nu mice. Pyridine derivative (LHT-17-19) was studied as water-soluble pharmaceutical substance. Acute toxicity was evaluated in groups of 5 animals, and the results were analyzed by Finney. Antitumor and antimetastatic activity was studied in syngeneic and xenograft models of lung cancer in mice.
 Results and discussion: LHT-17-19 belongs to class 3 of the toxicity classification of chemicals in accordance with GOST 12.1.007–76. The substance demonstrated an antitumor and antimetastatic property in mice with syngeneic tumor Lewis lung carcinoma as well as on the heterotopic tumor model of non-small cell lung cancer in humanized animals.
 Conclusion: LHT-17-19 belongs to class 3 of the toxicity classification of chemicals in accordance with WHO recom­mendation. LHT-17-19 exerts antitumor and antimetastatic property on both syngeneic and patient-derived lung cancer xenograft murine models.
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PH-Responsive PEGylated Niosomal Nanoparticles as an Active-Targeting Cyclophosphamide Delivery System for Gastric Cancer Therapy.

A PEGylated niosomal formulation of cyclophosphamide (Nio-Cyclo-PEG) was prepared using a central composite design and characterized in terms of drug loading, size distribution, and average size. The stability of formulations was also studied at different conditions. In vitro cytotoxicity of drug delivery formulations was assessed on gastric cancer cells using MTT assay. The mechanism of cytotoxicity was studied at the transcriptional level by real-time PCR on Caspase3, Caspase9, CyclinD, CyclinE, MMP-2, and MMP-9 genes, while apoptosis was investigated with flow cytometry. The anti-metastatic property was evaluated using the scratch method. Propidium iodide staining was used to study the cell cycle. The results indicated that the as-designed nanocarrier exhibited a controlled drug release pattern with improved nanoparticle stability. It was found that the living cancer cells treated with Nio-Cyclo-PEG showed a significant decrease in number when compared with the niosomal carrier without PEG (Nio-Cyclo) and free drug (Cyclo). Moreover, the drug-loaded nanocarrier induced planned death (apoptosis) in the cancer cells through the regulation of Caspase3, Caspase9, CyclinD, CyclinE, MMP-9, and MMP-2 gene expression, indicating that the Nio-Cyclo-PEG formulation could significantly inhibit the cell cycle at the sub G1 phase as well as prevent the migration of cancer cells. In conclusion, Nio-Cyclo-PEG as developed in this study could serve as an active-targeting drug delivery nanocarriers for gastric cancer therapy with high efficacy and minimal side effects on healthy tissues/cells.

ANTIMETASTATIC POTENTIAL OF CUCUMIN IN ANAPLASTIC THYROID CANCER AND COMBINED ACTIVITY WITH DOCETAXEL

Anaplastic thyroid cancer (ATC) is one of the deadliest human malignancies, with no effective treatment, survival limited to a few months. The disease is characterized by a high rate of metastasis and is resistant to almost all available cytotoxic. There is an urgent need for chemicals with an effective, low toxicity profile. Objective: In study, the antimetastatic property of tetrahydrocurcumin (THC), the active metabolite of Curcuma Longa, was compared with docetaxel and the presence of synergism in the combination of the two substances was investigated in vitro. Material and Method: IC25 and IC50 concentrations of THC and (DX) in CAL62 and 8505C cells were determined by modified MTT method we developed in our laboratory. These 2 concentrations were compared with the control in the treatment groups. Cell motility as an indicator of metastatic potential was evaluated by in-vitro wound healing method. Cellular cytotoxicity was evaluated by TAS-TOS analyses. Results: In the 8505C cell line, Total antioxidant status was observed in the DXB-CRC IC50/2 group with a significant statistical increase. THC significantly reduced the oxidative stress index in the highest combination group, especially in DXB. It was found that the combined dose prevented migration and invasion in CAL62 cells in the first hours. There was no difference in Total Oxidant level between the combination and control groups. It was observed that the most effective dose that significantly reduced the oxidative level was DX50. THC in ATK cells has antimetastatic potential close to Docetaxel; It was thought that docetaxel reduced oxidative stress.

Studies on the mode of action of synthetic diindolylmethane derivatives against triple negative breast cancer cells.

Diindolylmethane (DIM) is a metabolic product of indole-3-carbinol (I3C), the major phytochemicals present in cruciferous vegetables, which can modulate multiple signalling pathways in cancer. The present study deals with the mechanism of action of two synthetic biaryl conjugates of DIM in triple negative breast cancer cells. Out of 12 DIM derivatives tested, two compounds, DIM-1 and DIM-4, exhibit cytotoxicity with GI50 values of 9.83 ± 0.2195 μM and 8.726 ± 0.5234 μM, respectively, in 2D culture. In 3D culture, DIM-1 and DIM-4 show GI50 values of 24.000 ± 0.7240 μM and 19.230 ± 0.3754 μM, respectively. The non-toxic nature of the compounds was also established by the toxicity studies using the zebrafish model system. The two compounds induced apoptosis and anoikis in the cancer cells, which was confirmed by morphological analysis, nuclear fragmentation, membrane integrity assay, caspase activity measurements and modulation of pro/anti-apoptotic proteins. The compounds inhibited cell migration and MMP-2 and MMP-9 activities indicating their anti-metastatic property. They also reduced the expression of active Ras, phosphorylated forms of PI3K, Akt and mTOR. Immunofluorescence studies revealed the reduced expression of EGFR and pEGFR in treated cells. To conclude, DIM-1 and DIM-4 induced anti-breast cancer effects by blocking EGF receptor and subsequently inhibiting Ras-mediated PI3K-Akt-mTOR signalling pathway.

Anti-metastatic Potential of Natural Triterpenoid Cucurbitacin B Against Cholangiocarcinoma Cells by Targeting Src Protein.

Owing to the crucial role of Src in cancer metastasis, interruption of Src and its signaling has been considered a promising strategy for cancer metastasis treatment. Cucurbitacin B, a dietary triterpenoid, has been shown to possess anti-proliferative and apoptosis-inducing activities in cholangiocarcinoma (CCA) cells via suppressing the activation of FAK which is a main downstream Src effector. We hypothesized that cucurbitacin B might act as a Src suppressant which conferring anti-metastasis effect against CCA cells. To investigate this, the role of Src in regulating metastasis behavior of CCA cells and the effect of cucurbitacin B on Src-mediated metastatic phenotype of these cells were determined. The results showed that activation of Src significantly enhanced the migratory and invasive abilities of CCA cells. Molecular analysis revealed that Src-facilitated metastasis behavior of CCA cells occurred by modifying expression of a wide range of metastasis-related genes in the cells. Consistent with gene expression results, activation of Src significantly induced the protein expression of 2 important metastasis-associated molecules, MMP-9 and VEGF. Cucurbitacin B markedly suppressed activation of Src and its key effector, FAK. As a consequence, the alteration of expression profiles of metastasis-associated genes induced by Src activator in CCA cells was diminished by cucurbitacin B treatment. The compound also down-regulated Src-induced expression of MMP-9 and VEGF proteins in the cells. Moreover, molecular docking analysis revealed that cucurbitacin B could interact with Src kinase domain and possibly restrain the kinase from being activated by hindering the ATP binding. In conclusion, cucurbitacin B exhibited anti-metastatic property in CCA cells via negatively influencing Src and Src-related oncogenic signaling. This compound may therefore be a potential therapeutic drug for further development as an anti-Src agent for treatment of metastatic CCA.

Securinine induces mitotic block in cancer cells by binding to tubulin and inhibiting microtubule assembly: A possible mechanistic basis for its anticancer activity

AimAnalysis of the anticancer and antimitotic activity of the plant derived alkaloid securinine along with its effect on the organization of cellular microtubules as well as its binding with purified goat brain tubulin in-vitro. Materials and methodsThe cytotoxicity of securinine on different cell lines was conducted using SRB assay. The effect of securinine on the cellular microtubules was analyzed using immunofluorescence microscopy. The binding of securinine on purified goat brain tubulin was evaluated using fluorescent spectroscopy. Key findingsSecurinine effectively prevented the proliferation of cervical, breast and lung cancer cells with an IC50 of 6, 10 and 11 μM respectively and induced minimal toxicity in HEK cell line. Securinine at concentrations higher than IC50 induced significant depolymerization in interphase and mitotic microtubules and it suppressed the reassembly of cold depolymerized spindle microtubules in HeLa cells. In the wound healing assay, securinine effectively suppressed the migration of HeLa cells to close the wound. Securinine bound to tubulin with a Kd of 9.7 μM and inhibited the assembly of tubulin into microtubules. The treatment with securinine induced a mitochondrial dependent ROS response in HeLa cells which enhanced the cytotoxic effect of securinine. The result from gene expression studies indicates that securinine induced apoptosis in MCF-7 cells through p53 dependent pathway. SignificanceConsidering the strong anticancer and anti-metastatic property and low toxicity in non-malignant cell lines, we suggest that securinine can be used as a chemotherapeutic drug either alone or in combination with other known anticancer molecules.

Pterostilbene-isothiocyanate inhibits breast cancer metastasis by selectively blocking IKK-β/NEMO interaction in cancer cells

Metastasis, the main cause of breast cancer-associated fatalities, relies on many regular pathways involved in normal cell physiology and metabolism, thus, making it challenging to identify disease-specific therapeutic target(s). Chemically synthesized anti-metastatic agents are preferred for their fast and robust actions. However, these agents have adverse side effects, thus, increasingly favouring the identification of phytocompounds as suitable alternatives. Resveratrol and pterostilbene have long been established as potent anti-cancer agents. Earlier studies from our laboratory documented the anti-cancer activities associated with pterostilbene-isothiocyanate (PTER-ITC), a derivative of pterostilbene. The current study focuses on evaluating the anti-metastatic property of PTER-ITC and the underlying mechanism, by employing in silico, in vitro, and in vivo approaches. The significant anti-metastatic activity of PTER-ITC was observed in vitro against breast cancer metastatic cell line (MDA-MB-231) and in vivo in the 4T1 cell-induced metastatic mice model. Epithelial-mesenchymal transition (EMT), a hallmark of metastasis regulated by the transcription factors, Snail1 and Twist, was found to be reverted in vitro by PTER-ITC treatment. PTER-ITC blocked the activation of NF-κB/p65 and its concomitant nuclear translocation, resulting in the transcriptional repression of its target genes, Snail1 and Twist. PTER-ITC prevented the formation of IKK complex, central to NF-κB activation, by binding to the NEMO-binding domain (NBD) of IKK-β and inhibiting its interaction with NEMO (NF-κB essential modulator). According to our observations, PTER-ITC attenuated NF-κB activation selectively in cancerous cells. In conclusion, this study demonstrated that PTER-ITC is a potent anti-metastatic agent capable of targeting physiologically important pathways in a cancer-specific manner.

Moscatilin Inhibits Metastatic Behavior of Human Hepatocellular Carcinoma Cells: A Crucial Role of uPA Suppression via Akt/NF-κB-Dependent Pathway.

Hepatocellular carcinoma (HCC) frequently shows early invasion into blood vessels as well as intrahepatic metastasis. Innovations of novel small-molecule agents to block HCC invasion and subsequent metastasis are urgently needed. Moscatilin is a bibenzyl derivative extracted from the stems of a traditional Chinese medicine, orchid Dendrobium loddigesii. Although moscatilin has been reported to suppress tumor angiogenesis and growth, the anti-metastatic property of moscatilin has not been elucidated. The present results revealed that moscatilin inhibited metastatic behavior of HCC cells without cytotoxic fashion in highly invasive human HCC cell lines. Furthermore, moscatilin significantly suppressed the activity of urokinase plasminogen activator (uPA), but not matrix metalloproteinase (MMP)-2 and MMP-9. Interestingly, moscatilin-suppressed uPA activity was through down-regulation the protein level of uPA, and did not impair the uPA receptor and uPA inhibitory molecule (PAI-1) expressions. Meanwhile, the mRNA expression of uPA was inhibited via moscatilin in a concentration-dependent manner. In addition, the expression of phosphorylated Akt, rather than ERK1/2, was inhibited by moscatilin treatment. The expression of phosphor-IκBα, and -p65, as well as κB-luciferase activity were also repressed after moscatilin treatment. Transfection of constitutively active Akt (Myr-Akt) obviously restored the moscatilin-inhibited the activation of NF-κB and uPA, and cancer invasion in HCC cells. Taken together, these results suggest that moscatilin impedes HCC invasion and uPA expression through the Akt/NF-κB signaling pathway. Moscatilin might serve as a potential anti-metastatic agent against the disease progression of human HCC.

Furan-2-carboxamide derivative, a novel microtubule stabilizing agent induces mitotic arrest and potentiates apoptosis in cancer cells

The vital role played by microtubules in the cell division process, marks them as a potential druggable target to decimate cancer. A novel furan-2-carboxamide based small molecule, is a selective microtubule stabilizing agent (MSA) with IC50 ranging from 4 µM to 8 µM in different cancer cell lines. Inhibition of tubulin polymerization or stabilization of tubulin polymers abrogates chromosomal segregation during cell division, results in cell cycle arrest and leads to cell death due to the delayed repair mechanism. A novel furan-2-carboxamide based small molecule exhibited potent anti-proliferative and anti-metastatic property In-Vitro against the panel of cancer cells. Annexin V-FITC/PI, double staining reveals potent cytotoxic effect of SH09 against HeLa cells. FACS analysis displays induction of G2/M arrest and accumulation of subG1 population of cells upon treatment with SH09. Molecular docking study unveils SH09 binding affinity to the Taxol binding pocket of tubulin proteins and MM-GBSA also confirms strong binding energies of SH09 with tubulin proteins.

EnDuo, a novel derivative of Endostar, inhibits the migration of colon cancer cells, suppresses matrix metalloproteinase-2/9 expression and impedes AKT/ERK activation

Background/aimsColon cancer remains a life-threating disease with increasing morbidity and mortality worldwide despite the advancement in modern medical treatment. Therefore, novel and effective anti-colon cancers drugs are urgently needed. In this study, we investigated the anti-metastatic property EnDuo, a modified version of Endostar, and the underlying mechanisms. MethodsColon cancer cells were treated with different concentrations of EnDuo (50 μg/mL, 100 μg/mL, 200 μg/mL), and Endostar (100 μg/mL) as positive control. Cell Counting Kit-8 assay was performed to test the effect of EnDuo on cell viability. A scratch wound assay and transwell assay were employed to evaluate the relocation and motility of malignant colon cells following treatment with EnDuo. Western blot analysis was used to determine inhibitory effects of EnDuo by detecting the phosphorylation level of AKT and ERK proteins, and the expression of MMP-2 and MMP-9 proteins. ResultsOur results showed that EnDuo impedes the migration of colon cancer cells in a dose-dependent manner. At the molecular level, EnDuo induced a significant reduction in the phosphorylation of AKT and ERK proteins, and inhibited the expression of MMP-2 and MMP-9 proteins. ConclusionsCollectively, these results demonstrate that EnDuo exhibits a comparable anti-metastatic effect by suppressing the migration of colon cancer cells. Possibly, EnDuo interrupts the PI3K/AKT/ERK signaling pathway to arrest cell migration. Our study provides a novel insight to the potential clinical applications of EnDuo against colon cancers in the future.

Targeting TGF-β-Mediated SMAD Signaling Pathway via Novel Recombinant Cytotoxin II: A Potent Protein from Naja naja oxiana Venom in Melanoma.

Since the current treatments have not resulted in the desired outcomes for melanoma patients, there is a need to identify more effective medications. Together with other snake venom proteins, cytotoxin-II has shown promising results in tumoral cells. In this study, recombinant cytotoxin-II (rCTII) was expressed in SHuffle® T7 Express cells, while the epitope mapping of rCTII was performed to reveal the antibody-binding regions of rCTII. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to assess the viability of SK-MEL-3 and HFF-2 cells after treating these cells with rCTII. The qRT-PCR was performed to evaluate the expression levels of matrix metallopeptidase 3 (MMP-3), SMAD2, SMAD3, caspase-8, caspase-9, and miR-214 in order to reveal the rCTII-induced signaling pathways in melanoma. Our results have shown that two regions of amino acids, 6–16 and 19–44, as predicted epitopes of this toxin, are essential for understanding the toxicity of rCTII. Treating the melanoma cells with rCTII substantially inhibited the transforming growth factor-beta (TGF-β)–SMAD signaling pathway and down-regulated the expression of MMP-3 and miR-214 as well. This cytotoxin also restored apoptosis mainly via the intrinsic pathway. The down-regulation of MMP-3 and miR-214 might be associated with the anti-metastatic property of rCTII in melanoma. The inhibitory effect of rCTII on the TGF-β signaling pathway might be associated with increased apoptosis and decreased cancer cell proliferation. It is interesting to see that the IC50 value of rCTII has been lower in the melanoma cells than non-tumoral cells, which may indicate its potential effects as a drug. In conclusion, rCTII, as a novel medication, might serve as a potent and efficient anticancer drug in melanoma.

The antilymphatic metastatic effect of hyaluronic acid in a mouse model of oral squamous cell carcinoma

ABSTRACTObjectives: Lymphatic metastasis is the main cause of low patient survival in cases of oral squamous cell carcinoma (OSCC). Several animal models have been established to uncover the mechanism that regulates lymph node metastasis of OSCC cells. Unfortunately, these models often take a long time to establish. The prolonged tumor burden can lead to animal cachexia, which may ultimately affect the experimental outcome. To overcome the disadvantages of these models, we established an orthotopic metastatic animal model of OSCC that showed quick lymph node metastasis potential.Results: DiR dye-labeled CAL27 cells were injected into tongue tissues of BALB/c nude mice, and the cells metastasized to lymph nodes on day 3. Metastasis was monitored using an in vivo imaging system and confirmed by histological observation. Using this model, we investigated the role of hyaluronic acid (HA) on the cervical metastasis of OSCC cells. Surprisingly, we found that the presence of HA significantly reduced the incidence of metastasis to cervical lymph nodes compared with the control group. Further analysis revealed that the presence of exogenous HA promoted mesenchymal-epithelial transition (MET) in primary tumors while reducing the metastatic potential of OSCC.Conclusion: Our findings confirmed the establishment of a fast and reliable lymphatic metastatic mouse model of OSCC that can be used for investigating metastatic mechanisms and analyzing various antimetastasis strategies. An equally important discovery is the antimetastatic property of HA, which could provide a potential therapeutic strategy for OSCC.

NIR triggered PLGA coated Au-TiO2 core loaded CPT-11 nanoparticles for human papillary thyroid carcinoma therapy

MDR (multi-drug resistance) is one of the significant deterrents of effective chemotherapy for malignant growth. One of the powerful ways to deal with defeat of the MDR is to utilize inorganic nanoparticle-intervened tranquilize conveyance to build the medication aggregations in cancerous growth cells. In this work, we have developed the presentation that is accurately made of medication conveyance framework dependent on the TiO2 nanoparticles stacked CPT-11 to defeat the thyroid malignancy cells. The synthesized nanoparticles are characterized by spectroscopy methods (UV–vis, XPS, SEM, TEM, and DLS). The TEM results suggested that the shape of PLGA-Au-TiO2@CPT-11 of nanoparticles is ∼250 nm. After successful synthesis, we have evaluated the MTT of PLGA-Au-TiO2@CPT-11 nanoparticles with and without NIR radiations. Further, the morphological changes were observed using various biochemical stainings, such as acridine orange and ethidium bromide (AO–EB) and nuclear staining through Hoechst-33258. Also, migration and cell invasion were examined. The results show that these PLGA-Au-TiO2@CPT-11 and PLGA-Au-TiO2@CPT-11 + NIR nanoparticles exhibited promising antimetastatic property and reduced the cell invasion activity in B-CPAP and FTC-133 thyroid cancer cell lines. Based on the above findings, these PLGA-Au-TiO2@CPT-11 and PLGA-Au-TiO2@CPT-11 + NIR nanoparticles can be used as a promising candidate for the malignant thyroid cells.

Apoptotic induction and anti-metastatic activity of eugenol encapsulated chitosan nanopolymer on rat glioma C6 cells via alleviating the MMP signaling pathway

Glioma is the prime cause of cancer allied mortality in adolescent people and it accounts about 80% of all malignant tumours. Eugenol is a major bioactive constituent present in the essential oils with numerous pharmacological benefits including nueroprotective activity. The major drawback of eugenol is its extreme volatile property and oxygen sensitivity therefore we increased the efficacy of drug; eugenol by encapsulating with chitosan polymer. Eugenol loaded chitosan polymer (EuCs) was characterized using FTIR, XRD, SEM, HR-TEM analysis and the encapsulation, drug release efficacy was assessed at in vitro condition. The induction of autophagy and anticancer efficacy of EuCs on glioma cells was evaluated with rat C6 glioma cells using MTT assay, acridine orange staining, immunocytochemical analysis of NFκβ protein expression and FLOW cytometric analysis. The anti-metastatic property of Eu-CS was assessed by immunoblotting and RT-PCR analysis of epithelial mesenchymal transition protein expression in EuCs treated rat C6 glioma cells. Our characterization analysis proves that EuCs possess essential physical and functional properties of copolymer to be utilized as a drug. Further the MTT analysis and AO staining confirms even in the presence of oncogenic inducer and autophagic inhibitors, EuCs exhibits apoptotic potency on rat C6 glioma cells. The result of immunocytochemical studies depicts the inhibition of NFκβ protein expression and flow cytometry studies confirm apoptosis induction by EuCs. The inhibition of metastasis by EuCs was proven by the decrease in epithelial mesenchymal transition protein expression inEu-Cs treated rat C6 glioma cells. Over all our results authentically confirms eugenol loaded chitosan nanopolymer persuasively induces apoptosis and inhibits metastasis in rat C6 glioma cells.

Targeted suppression of metastasis regulatory transcription factor SOX2 in various cancer cell lines using a sequence-specific designer pyrrole–imidazole polyamide

Metastasis, a deadly feature of cancer, compromises the prognosis and accounts for mortality in the majority of cancer patients. SOX2, a well-known pluripotency transcription factor, plays a central role in cell fate determination and has an overlapping role as a regulatory factor in tumorigenesis and metastasis. The demand is increasing for clinically useful strategies for artificial control of SOX2 expression and its complex transcription machinery in cancer cells. N-Methylpyrrole (Py) and N-methylimidazole (Im) polyamides are small programmable designer ligands that can be pre-programmed to selectively recognize DNA sequence and control endogenous gene expression. Herein, we evaluated the anticancer activity of a designer ligand (SOX2i). SOX2i remarkably altered the expression of SOX2 at the mRNA and protein level in human cancer cell lines such as SW620 (colorectal adenocarcinoma), MKN45 (gastric adenocarcinoma), MCF7 (breast carcinoma), U2OS (osteosarcoma) and other cancer cell lines of different origin and type. Genome-wide transcriptome analysis and cell-based assays showed SOX2 to be a downregulated upstream regulator that alters cell proliferation, cell cycle progression, metabolism and apoptotic pathway. Studies in the mouse model confirmed the anti-metastatic property of SOX2i. SOX2i inhibited the expression of genes associated with EMT and stemness. Moreover, Wnt-canonical signaling was found to be downregulated in the SOX2i-treated group. Our proof-of-concept study supports the potential of DNA-based programmable small molecules for controlling the key regulatory factors associated with tumorigenesis and metastasis.

Prognostic significance of metastasis-suppressor gene NM23 in gastric carcinoma

Aim: Metastasis is critical in the prognosis of gastric cancer patients and in deciding on treatment strategies. Therefore, studies have concentrated on metastasis suppressor genes. This study aimed to identify the characteristics of NM23 expression in gastric cancer and to investigate its anti-metastatic and prognostic significance.Methods: Ninety patients who underwent surgery for gastric cancer between January 1, 2009 and January 1, 2010 were included in this study. Immunohistochemical staining was applied to specimen sections. The results of the immunohistochemical staining were evaluated with the normal gastric mucosa adjacent to the tumor. The degree of NM23 staining of tumor cell compared to the normal tissue was evaluated in two groups of “negative-weak staining” and “strong staining”. Both groups were analyzed for lymph node metastasis, vascular invasion, perineural invasion, degree of tumor differentiation, tumor stage and distant metastasis.Results: Among 58 patients with lymph node metastasis, 70.7% showed negative-weak staining and 29.3% showed strong staining. Among 32 patients with no lymph node metastasis, 40.6% had negative-weak staining and 59.4% had strong staining. Decrease in NM23 expression was shown to cause an increase in lymph node metastasis (P=0.01). Furthermore, while there was no statistical significance, the rates of distant metastasis, degree of poor differentiation, tumors in stage III and stage IV were apparently higher in the negative-weak staining group. These results were in line with the anti-metastatic property of NM23. Conclusion: This study showed that NM23 expression had anti-metastatic properties for lymph node metastasis in gastric cancer patients.