Colon Cancer Drug Research Articles

Lactobacillus casei JY300-8 generated by 12C6+ beams mutagenesis inhibits tumor progression by modulating the gut microbiota in mice

• A new mutant strain L. casei JY300-8 with excellent probiotic performance was generated by heavy ion beams irradiation induced-mutagenesis. • Probiotics JY300-8 was used for treat colon cancer and have a remarkable therapeutic effect in colon cancer mice. • JY300-8 was of better therapeutic effects, low treatment cost and less side effects compared to first-line therapy drug for cancer (DFUR) at an early state of colon cancer in mice. • JY300-8 significantly inhibited tumor progression by activating apoptosis of colon cells and regulating the gut microbiota in colon cancer mice. Probiotics, as novel functional foods via microbiota-modulation to enhance host health and inhibit tumor carcinogenesis, have been attracted considerable interests. L. casei JY, as a potential probiotic, was irradiated by 12 C 6+ beams and a new mutant strain JY300-8 was generated through three round selections of transit tolerance in the upper human gastrointestinal tract, adhesion ability to Caco-2 cells and inhibitory pathogenic microorganisms, respectively. Interestingly, JY300-8 presented excellent properties, including the strongest adhesion ability (86.81%) to Caco-2 cells to our knowledge and more excellent antimicrobial properties, which was used for the potential candidate probiotic. Additionally, JY300-8 could significantly inhibit the proliferation of Caco-2, HT29 and HCT116 cells in vitro, respectively. Furthermore, there were better therapeutic effects at an early stage in colon cancer mice, which included the similar survival rates (90%) and stronger inhibitory effect on tumor (83.48%), lower treatment cost and less side effects in comparison to the therapy drug (DFUR) for colon cancer (65.65%), which was attributed to promoting the apoptosis of colon cells and enhancing antitumor response via modulation cancer-induced gut microbiota dysbiosis by oral administration of JY300-8. Therefore, JY300-8 has great potential for bio-prophylactic and bio-therapeutic functional food in colon carcinogenesis. This work provided a promising approach that could improve human health, reduce greatly cancer incidence and mitigate cancer progression via modulation gut microbiota by excellent probiotics intervention.

Chitosan-Decorated PLGA-NPs Loaded with Tannic Acid/Vitamin E Mitigate Colon Cancer via the NF-κB/β-Cat/EMT Pathway.

Colon cancer is the second highest contributor of cancer-related deaths throughout the world. Treatment strategies with tannic acid and vitamin E are envisaged as desirable and safe owing to their robust antioxidative and anti-inflammatory potential. In the present report, these bioactives have been nanoencapsulated in poly(d,l-lactide-co-glycolic acid) (PLGA) formulations for maintaining sustained release and ensuring enhanced bioavailability. Capping of nanoparticles (NPs) with chitosan was done for enhanced anticancer efficacy and tumor targeting. CS-PLGA-TA-E, administered intraperitoneally, significantly inhibited tumor number and tumor volume and normalized colon histology in the colon cancer. Tissue distribution studies showed that TA/E content from CS-PLGA-TA-E was present in a higher concentration in the tumor tissue than the concentration of TA/E content from PLGA-TA-E or free TA or free E. Also, the TA/E content from all of the treatment groups showed its highest concentration in the tumor compared to other organs. Antioxidant enzymes and proinflammatory cytokines (TNF-α, IL-1β, IL-6) were inhibited by CS-PLGA-TA-E. CS-PLGA-TA-E inhibited markers for tumor growth (EGFR-PI3K-AKT), inflammation (NF-κB/Stat3), β-catenin signaling (β-catenin, c-myc, cyclin D1), EMT (E-cadherin, N-cadherin, vimentin), and apoptosis (Bcl-2) in a significantly greater way as compared with PLGA-TA-E, TA, or E. CS-PLGA-TA-E NPs can be considered promising anticancer drugs for colon cancer.

Impact of a Desmoplastic Tumor Microenvironment for Colon Cancer Drug Sensitivity: A Study with 3D Chimeric Tumor Spheroids.

Three-dimensional (3D) spheroid culture provides opportunities to model tumor growth closer to its natural context. The collagen network in the extracellular matrix supports autonomic tumor cell proliferation, but its presence and role in tumor spheroids remain unclear. In this research, we developed an in vitro 3D co-culture model in a microwell 3D (μ-well 3D) cell-culture array platform to mimic the tumor microenvironment (TME). The modular setup is used to characterize the paracrine signaling molecules and the role of the intraspheroidal collagen network in cancer drug resistance. The μ-well 3D platform is made up of poly(dimethylsiloxane) that contains 630 round wells for individual spheroid growth. Inside each well, the growth surface measured 500 μm in diameter and was functionalized with the amphiphilic copolymer. HCT-8 colon cancer cells and/or NIH3T3 fibroblasts were seeded in each well and incubated for up to 9 days for TME studies. It was observed that NIH3T3 cells promoted the kinetics of tumor organoid formation. The two types of cells self-organized into core-shell chimeric tumor spheroids (CTSs) with fibroblasts confined to the shell and cancer cells localized to the core. Confocal microscopy analysis indicated that a type-I collagen network developed inside the CTS along with increased TGF-β1 and α-SMA proteins. The results were correlated with a significantly increased stiffness in 3D co-cultured CTS up to 52 kPa as compared to two-dimensional (2D) co-culture. CTS was more resistant to 5-FU (IC50 = 14.0 ± 3.9 μM) and Regorafenib (IC50 = 49.8 ± 9.9 μM) compared to cells grown under the 2D condition 5-FU (IC50 = 12.2 ± 3.7 μM) and Regorafenib (IC50 = 5.9 ± 1.9 μM). Targeted collagen homeostasis with Sclerotiorin led to damaged collagen structure and disrupted the type-I collagen network within CTS. Such a treatment significantly sensitized collagen-supported CTS to 5-FU (IC50 = 4.4 ± 1.3 μM) and to Regorafenib (IC50 = 0.5 ± 0.2 μM). In summary, the efficient formation of colon cancer CTSs in a μ-well 3D culture platform allows exploration of the desmoplastic TME. The novel role of intratumor collagen quality as a drug sensitization target warrants further investigation.

In Silico Drug Design: Development of New Pyrimidine-based Benzothiazole Derivatives, Selective for CDK2

Backgroud: Kinases are proteins that control many biological functions. They are involved in cellular regulation, and many of them are deregulated in cancer proliferation. The evidence of this deregulation in many pathologies served as the origin of kinases as a therapeutic class and constitutes the motive that leads numerous teams to search for inhibitors of these targets. Objective: Based on 3D-QSAR studies and the molecular docking approach, we have developed new potential inhibitors that could be optimized and transformed into colon cancer drugs. Methods: To design new bioactive molecules and study their interactions with the cyclin-dependent kinase type 2 (CDK2) enzyme, we used two virtual screening methods: 3D-QSAR modeling and molecular docking on a series of 28 pyrimidine-based benzothiazole derivatives. Results: To develop the model (3D QSAR), we used CoMFA and CoMSIA techniques using SYBYLX2.0 molecular modeling software. The statistical parameters reveal that the good CoMFA model displays Q² = 0.587 and R²= 0.895 and CoMSIA displays Q² = 0.552 and R² = 0.768), which are considered to be very good internal prediction values, while an external validation of a test series of 5 compounds not included in the model development series gives R² test values of 0.56 for CoMFA and R² t est values of 0.51 for CoMSIA. The molecular docking approach with AutoDock Tools-1.5.6 is introduced in this work to enrich the interpretations extracted from the CoMFA and CoMSIA contour maps and to provide an in silico research method for the most favorable mode of interaction of an inhibitor within its receptor (CDK2). Conclusion: We have constructed and validated a quantitative 3D model of structure-activity relationships of pyrimidine-based benzothiazole derivatives as CDK2 inhibitors. This model allows us to identify the nature and position of the groups that enhance the activity, giving us directions to discover new, more powerful molecules in a limited time.

Evaluation of daidzein-loaded chitosan microcapsules for the colon cancer drug delivery: synthesis, characterization and release behaviour

Evaluation of daidzein-loaded chitosan microcapsules for the colon cancer drug delivery: synthesis, characterization and release behaviour

Eupatilin Impacts on the Progression of Colon Cancer by Mitochondria Dysfunction and Oxidative Stress

Colon cancer is one of the most frequently diagnosed cancer types. Some colon cancer cases resist standard anticancer drugs. Therefore, many studies have focused on developing therapeutic supplements using natural products with low side effects and broad physiological activity. Eupatilin is a flavonoid that is mainly extracted from artemisia and promotes apoptosis in numerous cancer types. However, since the current understanding of its physiological mechanisms on colon cancer cells is insufficient, we investigated how eupatilin affects the growth of two colon cancer cell lines, namely HCT116 and HT29. Our results showed that eupatilin inhibits cell viability and induces apoptosis accompanied by mitochondrial depolarization. It also induces oxidative stress in colon cancer cells and regulates the expression of proteins involved in the endoplasmic reticulum stress and autophagic process. Moreover, eupatilin may target the PI3K/AKT and mitogen-activated protein kinase (MAPK) signaling pathways in colon cancer cells. It also prevents colon cancer cell invasion. Furthermore, eupatilin has a synergistic effect with 5-fluorouracil (5-FU; a standard anticancer drug) on 5-FU-resistant HCT116 cells. These results suggest that eupatilin can be developed as an adjuvant to enhance traditional anticancer drugs in colon cancer.

Histopathology and Anticolon Cancer Effects of Turmeric Ethanolic Extracts in Wistar Rats

Colon cancer is cancer that begins in the large intestine. It usually begins as small, non cancerous clumps that form inside the colon. It typically affects older adults and can occur at any age. The aim of this study is to investigate the histopathological changes of the colon of rats experimentally induced with cadmium chloride as well as the anticancer effect of the ethanolic extract of Curcuma longa. Thirty six healthy albino rats of both sexes were classified into six groups with each group comprising of five rats as follows ; group I: normal control rats, group 2: Cadmium Chloride induced rats, group 3: Aduracil-5 fluorouracil treated rats, Group 4: dimethyl sulfuroxide treated rats, groups 5 and 6 rats were treated with 875mg/kg and 437.5mg/kg of Curcuma ethanolic extracts respectively after initial induction of cancer with cadmium chloride. Comparative observation of the cadmium induced colon showed histopathological damage as evidenced by empty goblet cells, lacerated and suppressed mucosa, destruction of the surface epithelium, features which were lacking in the control and Curcuma longa treated colon. Curcuma treated colon exhibited marked improvement of the histomorphology whilst cadmium treated colon clearly showed tumor cells, cancer cells or invasive inflammatory cells. Adruracil-5fluorouracil{an established anti colon cancer drugs} treated colon showed mild improvement in the histomorphology of the colon while the dimethyl sulfuroxide treated colon revealed an insignificant impact. The ameliorative effect on rat colon occasioned by administration of Curcuma ethanolic extract suggests that the plant product may have therapeutic activity against colon inflammation in albino rats.

Astragalin Inhibits the Proliferation and Migration of Human Colon Cancer HCT116 Cells by Regulating the NF-κB Signaling Pathway.

Astragalin is a flavonoid found in a variety of natural plants. It has anti-inflammatory, anti-oxidant effects and has inhibited effects against several malignant tumor cell types. However, its effects on colon cancer and the molecular mechanisms have remained to be elucidated. In this study, we evaluated the inhibitory effect of astragalin on proliferation and migration of human colon cancer HCT116 cells in vitro and in vivo. Furthermore, we elucidated the mechanism of these effects. The results showed that astragalin significantly inhibited the proliferation and diffusion of HCT116 cells by induced apoptosis (by modulation of Bax, Bcl-2, P53, caspase-3, caspase 6, caspase 7, caspase 8, caspase 9 protein express) and cell cycle arrest (by modulation of Cyclin D1, Cyclin E, P21, P27, CDK2, CDK4 protein express). Moreover, astragalin suppressed HCT116 cell migration by inhibiting the expression of matrix metalloproteinases (MMP-2, MMP-9). In addition, astragalin significantly downregulated the expression of key proteins in the NF-κB signaling pathway and inhibited the transcriptional activity of NF-κB P65 stimulated with inflammatory cytokines TNF-α, thereby inhibiting the growth of colon cancer cells in vitro. Our further investigations unveiled astragalin gavage significantly reduced the proliferation of colon cancer xenograft in nude mice, in vivo experiments showed that tumor growth was related to decreased expression of apoptotic proteins in tumor tissues and decreased activity of the NF-κB signaling pathway. In summary, our results indicated that astragalin inhibits the proliferation and growth of colon cancer cells in vivo and in vitro via the NF-κB pathway. Therefore, astragalin maybe become a potential plant-derived antitumor drug for colon cancer.

The critical role of peroxiredoxin-2 in colon cancer stem cells.

Colon cancer stem cells (CCSCs) play an important role in facilitating colon cancer occurrence, metastasis and drug resistance. The results of our previous studies confirmed that the well-studied antioxidant gene peroxiredoxin-2 (PRDX2) promotes colon cancer progression. However, the underlying function and mechanisms associated with PRDX2 remodeling in the context of CCSCs have remained poorly studied. In our present study, we demonstrated that PRDX2 is highly expressed in CD133/CD44-positive colon cancer tissues and spheroid CD133+CD44+ CCSCs. PRDX2 overexpression was shown to be closely correlated with CD133+CD44+ CCSCs in colon cancer. Furthermore, PRDX2 depletion markedly suppressed CD133+CD44+ CCSC stemness maintenance, tumor initiation, migration and invasion and liver metastasis. Furthermore, the expression of various EMT markers and Wnt/β-catenin signaling proteins was altered after PRDX2 inhibition. In addition, PRDX2 knockdown led to increased ROS production in CD133+CD44+ CCSCs, sensitizing CCSCs to oxidative stress and chemotherapy. These results suggest that PRDX2 could be a possible therapeutic target in CCSCs.

Gamma radiation synthesis of a novel amphiphilic terpolymer hydrogel pH-responsive based chitosan for colon cancer drug delivery

Particularly, chitosan (Cs) loaded with drug cannot pass through the colonic region, often leading in the bursting drug release in the stomach due to its solubility in gastric contents. The novelty of the current article is to solve this limitation by performing gamma irradiation cross-linking of Cs with two anionic polymers of (acrylic acid)-co-(2-acrylamido-2-methylpropane-sulfonic acid) (AAc/AMPS) to give amphiphilic hydrogel. The shifted in the characteristic FTIR peaks of Cs in the (Cs/AAc/AMPS) confirm the exits of inter-molecular interactions that make Cs and (AAc/AMPS) are miscible. Swelling experiments under different pH indicated that the (Cs/AAc/AMPS) hydrogels were significantly sensitive to pH change. The results give the possibility to use the obtained (Cs/AAc/AMPS) hydrogel on drug delivery system. The in vitro Fluorouracil (5-FU) releasing from (Cs/AAc/AMPS) matrix was examined under the influence of pH1 and pH7.The results confirmed the hydrogels capability to release 96 % of 5-FU drug at pH 7 after 7 h.

Colon Cancer Progression Is Reflected to Monotonic Differentiation in Gene Expression and Pathway Deregulation Facilitating Stage-specific Drug Repurposing.

Colon cancer is one of the most common cancer types and the second leading cause of death due to cancer. Many efforts have been performed towards the investigation of molecular alterations during colon cancer progression. However, the identification of stage-specific molecular markers remains a challenge. The aim of this study was to develop a novel computational methodology for the analysis of alterations in differential gene expression and pathway deregulation across colon cancer stages in order to reveal stage-specific biomarkers and reinforce drug repurposing investigation. Transcriptomic datasets of colon cancer were used to identify (a) differentially expressed genes with monotonicity in their fold changes (MEGs) and (b) perturbed pathways with ascending monotonic enrichment (MEPs) related to the number of the participating differentially expressed genes (DEGs), across the four colon cancer stages. Through an in silico drug repurposing pipeline we identified drugs that regulate the expression of MEGs and also target the resulting MEPs. Our methodology highlighted 15 MEGs and 32 candidate repurposed drugs that affect their expression. We also found 51 MEPs divided into two groups according to their rate of DEG content alteration across colon cancer stages. Focusing on the target MEPs of the highlighted repurposed drugs, we found that one of them, the neuroactive ligand-receptor interaction, was targeted by the majority of the candidate drugs. Moreover, we observed that two of the drugs (PIK-75 and troglitazone) target the majority of the resulting MEPs. These findings highlight significant genes and pathways that can be used as stage-specific biomarkers and facilitate the discovery of new potential repurposed drugs for colon cancer. We expect that the computational methodology presented can be applied in a similar way to the analysis of any progressive disease.

Mechanical characterization of bio composite films as a novel drug carrier platform for sustained release of 5-fluorouracil for colon cancer: Methodological investigation

In this study, we employed Pectin (PC) as a matrix that is hybridized with three different nucleobase (NB) units (cytosine, thymine, uracil) to generate pectin–nucleobase(PC-NB) biocomposite films stabilized through bio-multiple hydrogen bonds (BMHBs) as drug carrier for anticancer 5-Fluorouracil (5-FU). Prepared biocomposite films were characterized by Fourier Transform Infra-red Spectroscopy (FTIR), X-ray Diffraction (XRD), Thermogravimmetry Analysis (TGA) and Scanning Electron Microscope (SEM). Mechanical and sorption properties were also evaluated. In vitro drug release performed in both acidic pH 1.2 (stomach pH) and alkaline pH 7.4 (intestinal pH) showed that incorporation of nucleobases into pectin significantly restricted release rate of 5-FU particularly under acidic condition (pH 1.2). Hemolysis assays demonstrated that PC-NB-5-FU biocomposite film drug carriers were hemocompatible. Confocal microscope analysis indicates facilitated cellular uptake of PC-NB-5-FU film in HT-29 colon cancer cell line, which in turn result in a higher potential of apoptosis. Confocal imaging of fluorescent live/dead cell indicators and MTT assay outcomes, both demonstrated significant decreases in cellular viability of PC-NB-5-FU biocomposite films. Collectively, our findings indicate that this PC-NB-5-FU biocomposite films can be conferred as a proficient formulation for targeted delivery of colon cancer drugs.

Microbiota, Epigenética y respuesta a medicamentos en el cáncer de colon

El cáncer de colon es una de las principales causas de muerte a nivel mundial, en este sentido, a pesar de que se ha reducido la tasa de mortalidad, la incidencia en pacientes jóvenes sigue aumentando. El presente trabajo consiste en una revisión bibliográfica descriptiva de la relación existente entre la microbiota, la epigenética y la respuesta a medicamentos utilizados para tratar el cáncer de colon. Dicha revisión es elaborada a partir de la consulta de las bases de datos disponibles en la plataforma del Sistema de Bibliotecas, Documentación e Información (SIBDI) de la Universidad de Costa Rica. El objetivo central de este estudio es entender la relación existente entre la microbiota y la epigenética para así poder usar estos conocimientos en favor de la optimización de la terapia farmacológica y, además, predecir respuestas a medicamentos en el cáncer de colon. Se encontró evidencia que sugiere que el tipo de dieta impacta directamente en la microbiota intestinal, la cual, por su parte, puede tener un efecto pro o anti cancerígeno, dependiendo de las modificaciones epigenéticas dadas por metabolitos de estas bacterias y que pueden modificar la respuesta a la quimioterapia. Se concluye que el cáncer de colon es de origen multifactorial, por lo que se afirma que se ve afectado por eventos genéticos: la dieta, el estilo de vida, la microbiota y sus metabolitos. Finalmente, es promisorio encontrar maneras para asociar concretamente microbiota relacionada con los cambios de respuesta a medicamentos y así optimizar las terapias oncológicas.

Curcumin may be a potential adjuvant treatment drug for colon cancer by targeting CD44

Despite the considerable advances in treatment method development, the mortality rate related to colon cancer still ranks the fifth in all tumor-related diseases. Recently, there has been growing evidences supporting the existence of colon cancer stem cells (CSCs) might be one of the main causes for initiation, progression and recurrence of colon cancer. Curcumin has been shown to possess anticancer activities. It has also been suggested that curcumin was effective against colon CSCs by coupling with CD44, a robust marker and functional important molecule for colorectal CSC. In the present study, we confirmed that curcumin can inhibit the proliferation, colony formation, migration and tumor sphere formation of colon cancer cells. Results from real-time PCR and western blotting had suggested that curcumin could down-regulate the expression of CD44. Moreover, results from flow cytometry had further revealed that curcumin could decrease the proportion of CD44+ colon cancer cells. After the expression of CD44 had been knocked down by using siRNA, the inhibition effects of curcumin against CD44+ colon cancer cells were observed to be reduced significantly. Moreover, it had been observed that the cellular uptake of curcumin was significantly higher in CD44+ colon cancer cells. Results from flow cytometry had shown that curcumin could induce apoptosis in CD44+ colon cancer cells. Altogether, our results suggested that curcumin might be an adjuvant drug for the treatment of colorectal cancer by targeting CD44.

Immunogenic chemotherapy in two mouse colon cancer models.

Aside from the induction of cell death, some anticancer chemotherapeutic drugs can modulate antitumor immune responses. In this study, we examined the anticancer effects of 5‐fluorouracil (5‐FU) and oxaliplatin (L‐OHP), which are standard chemotherapeutic drugs for colon cancer, combined with cyclophosphamide (CP) in two mouse colon cancer models (CT26 and MC38 colon adenocarcinoma models). In the CT26 model, two injections of 5‐FU/L‐OHP and CP significantly suppressed the growth of subcutaneously established CT26 tumors compared with either 5‐FU/L‐OHP or CP, without a significant loss of body weight. The anticancer effect was weakened in nude mice. Cured mice acquired protective immunity against CT26, and CT26‐specific cytotoxic T cells (CTLs) were induced from their spleen cells. Analysis of tumor‐infiltrating immune cells revealed that 5‐FU/L‐OHP treatment with or without CP increased the proportion of CD8+ T cells at tumor sites. The 5‐FU/L‐OHP treatment decreased the proportion of granulocytic myeloid‐derived suppressor cells (MDSCs) and increased monocytic MDSCs in tumor sites, whereas the addition of CP treatment reversed these changes. In the MC38 model, although significant anticancer effects of the triple combination therapy were seen, additional treatment with anti‐PD‐1 antibody increased the number of cured mice. These mice exhibited protective immunity against MC38, and MC38‐specific CTLs were generated from their spleen cells. Together, these results indicate that the antitumor effects of the combination of 5‐FU/L‐OHP and CP mainly depend on host T cells; moreover, the therapeutic efficacy can be effectively boosted by immune checkpoint blockade.

Cyclometallated gold(III) complexes against colon cancer. X-ray structure of [Au(C,NPhenylpyridine)(OAc)2

The discovery of cisplatin made a difference in the way that chemotherapy was understood. Since then, and in order to improve the effectiveness and the clinical problems related to this kind of metallodrugs, several metals have been investigated as an alternative to this therapy. Due to the chemical similarities with Pt(II), Au(III) is a promising metal for this purpose. Nevertheless, the stabilization of this oxidation state in physiological conditions is still a difficult goal to achieve. In this research, we have studied the cyclometallation as a strategy to make stable Au(III) complexes, and we have evaluated these compounds as candidates to be used in the treatment of colon cancer. To achieve our goals, we made a huge effort to design a general strategy to obtain cycloaurated complexes, without organomercurial compounds. Thus, we have synthesized the cyclometallated Au(III) derivatives from the corresponding [AuCl3(N–CH)] complex and we have tested some ADME-tox properties of these compounds. The partition coefficient showed that, although [AuCl3(N–CH)] were more water-soluble, cyclometallated species present a better balance between hydro- and lipophilicity. That is why cycloaurated complexes were modified by the coordination of O-donor ligands and studied as anticancer drugs for colon cancer (Caco-2/TC7 cell line). The precursors ([AuCl3(N–CH)]) and starting cyclometallated complexes did not present any effect on tumour or normal cell proliferation. However, complex [Au(Phe)(ppy)]Cl presents a better antiproliferative effect than cisplatin on tumour cells and a selectivity 9-times greater towards tumour cells than towards normal cells. Some interesting conclusions actually arise from these results for a better future structural design, and thus to achieve more active anticancer drugs.

Large-scale label-free single-cell analysis of paramylon in Euglena gracilis by high-throughput broadband Raman flow cytometry.

Microalga-based biomaterial production has attracted attention as a new source of drugs, foods, and biofuels. For enhancing the production efficiency, it is essential to understand its differences between heterogeneous microalgal subpopulations. However, existing techniques are not adequate to address the need due to the lack of single-cell resolution or the inability to perform large-scale analysis and detect small molecules. Here we demonstrated large-scale single-cell analysis of Euglena gracilis (a unicellular microalgal species that produces paramylon as a potential drug for HIV and colon cancer) with our recently developed high-throughput broadband Raman flow cytometer at a throughput of >1,000 cells/s. Specifically, we characterized the intracellular content of paramylon from single-cell Raman spectra of 10,000 E. gracilis cells cultured under five different conditions and found that paramylon contents in E. gracilis cells cultured in an identical condition is given by a log-normal distribution, which is a good model for describing the number of chemicals in a reaction network. The capability of characterizing distribution functions in a label-free manner is an important basis for isolating specific cell populations for synthetic biology via directed evolution based on the intracellular content of metabolites.

Associations Between miRNAs and Two Different Cancers: Breast and Colon.

ObjectiveScreening approaches using microRNAs (miRNAs) have been gaining increased attention owing to their potential applications in the diagnosis, prognosis, and monitoring of cancer, because aberrant miRNA expression plays a role in the development and advancement of malignancies. The objectives of this study were to characterize mir21, miR31, mir143, mir145, and control RNU43, which are differentially expressed in peripheral blood mononuclear cells (PBMCs) of breast and colorectal cancer patients, compared to that in controls and to establish whether this is specific to breast and colon cancer for use as tumor markers.MethodsThirty newly diagnosed patients with breast cancer and 30 patients with colorectal cancer were enrolled together with 30 healthy controls. PBMCs were isolated from venous blood samples of individuals. Next, miRNA expression analysis was performed by a two-step method of reverse transcription and qPCR.ResultsThe expression levels of miR-143 and miR-31 were significantly decreased, whereas the expression levels of miR-145 and miR-21 were significantly increased in breast cancer patients compared to those in healthy subjects. Moreover, the expression levels of miR-143, miR-145, and miR-21 were significantly increased and, in contrast, the changes in the expression levels of miR-31 were not statistically significant in colon cancer compared to those in healthy subjects. miR-21 exhibited the highest increase in both breast and colon cancers. There was a weak positive correlation between miR-145 and CA-15.3 in patients with breast cancer (r = 0.451; p = 0.012). miR-143 was positively correlated with the TNM stage in colon cancer patients (r = 0.568; p = 0.001).ConclusionA biomarker panel composed of miR-21, miR-31, miR-143, and miR-145 in PBMC may provide a new diagnostic approach for the early detection of breast and colon cancer. As miR-21 expression was found to be the highest among all the miRNAs evaluated, it may represent a new tumor biomarker and a candidate therapeutic drug or gene target in colon and breast cancer.

Docetaxel-Loaded Disulfide Cross-Linked Nanoparticles Derived from Thiolated Sodium Alginate for Colon Cancer Drug Delivery.

In this study, fluorescein-labelled wheat germ agglutinin (fWGA)-conjugated disulfide cross-linked sodium alginate nanoparticles were developed to specifically target docetaxel (DTX) to colon cancer cells. Different amounts of 3-mercaptopropionic acid (MPA) were covalently attached to sodium alginate to form thiolated sodium alginate (MPA1–5). These polymers were then self-assembled and air-oxidised to form disulfide cross-linked nanoparticles (MP1–5) under sonication. DTX was successfully loaded into the resulting MP1–5 to form DTX-loaded nanoparticles (DMP1–5). DMP2 had the highest loading efficiency (17.8%), thus was chosen for fWGA surface conjugation to form fWGA-conjugated nanoparticles (fDMP2) with a conjugation efficiency of 14.1%. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses showed spherical nanoparticles, and an in vitro drug release study recorded a cumulative drug release of 48.6%. Dynamic light scattering (DLS) analysis revealed a mean diameter (MD) of 289 nm with a polydispersity index (PDI) of 0.3 and a zeta potential of −2.2 mV for fDMP2. HT-29 human colon cancer cells treated with fDMP2 showed lower viability than that of L929 mouse fibroblast cells. These results indicate that fDMP2 was efficiently taken up by HT-29 cells (29.9%). Fluorescence and confocal imaging analyses also showed possible internalisation of nanoparticles by HT-29 cells. In conclusion, fDMP2 shows promise as a DTX carrier for colon cancer drug delivery.

Protosappanin B Exerts Anti-tumor Effects on Colon Cancer Cells via Inhibiting GOLPH3 Expression.

Protosappanin B (PSB) is a key active component of Lignum Sappan extract. Although the antiproliferative effects of Lignum Sappan extract have been demonstrated in various cancer cells, relatively little is known about the effects of PSB on tumor progression. The aim of this study was to explore the anti-tumor effects of PSB on human colon cancer cells by regulation of intracellular signaling pathways and Golgi phosphoprotein 3 (GOLPH3) expression in vitro and in vivo. Our results showed that PSB effectively inhibited the viability and migration of SW620 cells and induced apoptosis, but had poor effect on HCT116 cells. Furthermore, PSB significantly reduced the expression of p-AKT, p-p70S6K, β-catenin, and p-ERK1/2 proteins in SW620 cells, and this effect was reversed by the corresponding signaling pathway agonists. Interestingly, PSB could also suppress GOLPH3 expression of SW620 cells in a concentration-dependent manner, but SW620 cells transfected with lentiviral vectors overexpressing GOLPH3 can effectively resist the cytotoxic activity of PSB in vitro. The xenograft experiment of SW620 cells with LV-GOLPH3 confirmed that PSB distinctly inhibited the tumor growth via suppressing GOLPH3 expression. Collectively, these findings clarified a new anti-cancer mechanism of PSB through inhibition of GOLPH3 expression and intracellular signaling pathways in colon cancer cells. PSB may be a potential new drug for colon cancer.