Apoptosis In Colon Cancer Cells Research Articles

Effect of RNF152 on NO induced apoptosis of colon cancer cells

Objective: To investigate the role and mechanism of ring finger protein 152 (RNF152) in the development of colitis-associated colon cancer (CAC). Methods: CAC was induced by azoxymethane (AOM) and dextran sulfate sodium (DSS) in C57BL/6 mice. Three different stages of mice during the development of colon cancer were obtained, named AD1, AD2 and AD3, respectively. A control group of mice without any treatment was set up as well. The expression of RNF152 in mouse colon tissues was measured by real-time quantitative polymerase chain reaction (RT-qPCR). The effects of RNF152 overexpression on apoptosis and nitric oxide (NO) induced apoptosis was examined by flow cytometry. The expressions of Bcl-2 and Bcl-XL were detected by western blot. Results: CAC was effectively induced by AOM and DSS in C57BL/6 mice. The tumor incidence rate of AD3 group was 100%. The whole genome expression microarray data from mouse AOM-DSS model indicated that the mRNA level of RNF152 was gradually decreased during the development of colon cancer. The RT-qPCR results showed that RNF152 mRNA level in AD3 was 1.23±0.18, higher than 0.52±0.08 in negative control (P<0.01). Flow cytometry analysis showed that overexpression of RNF152 increased the apoptosis of RKO cells (P<0.01). The apoptotic rate of RKO-RNF152 cells treated with NO donor DETA NONOate was (31.2±3.1)%, higher than (14.2±2.1)% in RKO-PCDB cells (P<0.001). Overexpression of RNF152 significantly decreased the protein expressions of Bcl-XL and Bcl-2. Conclusion: Downregulation of RNF152 may facilitate the development of CAC by inhibiting the cell apoptosis.

Verbesina encelioides-induced cytotoxicity and mitochondria-mediated apoptosis in human colon cancer cells through ROS generation

Verbesina encelioides-induced cytotoxicity and mitochondria-mediated apoptosis in human colon cancer cells through ROS generation

Aberrant expression of LncRNA CASC2 mediated the cell viability, apoptosis and autophagy of colon cancer cells by sponging miR‐19a via NF‐κB signaling pathway

Abnormal and rapid proliferation of colon cancer cells is a severe problem that can be regulated by non-coding RNAs. Thus, our study focused on effects of lncRNA CASC2 and miR-19a on colon cancer cells. Expressions of lncRNA CASC2, miR-19a, Bcl-2, Bax and NF-κB/p65 were examined by RT-qPCR. Cell viabilities were detected by CCK-8. A luciferase report assay was used for measuring binding conditions between lncRNA CASC2 and miR-19a. Western blotting was used to evaluate expression of LC3-I, LC3-II and p62 related to autophagy. Expression of lncRNA CASC2 lower in cancer cell lines and the overexpression reduced the cell viability of HT29 and SW480. Furthermore, Bcl-2 was suppressed by overexpressed lncRNA CASC2, while Bax was upregulated. LC3-Ⅰ and p62 were both inhibited, but LC3-Ⅱ was promoted. MiR-19a was predicted to bind lncRNA CASC2 and expressed higher in cancer cell lines. Overexpressed miR-19a reduced expression of lncRNA CASC2 and increased cell viability. This was repressed by upregulated lncRNA CASC2. Bcl-2 and Bax expression and proteins implicated in autophagy that are regulated by lncRNA CASC2 upregulation were reversed by miR-19a overexpression. NF-κB was upregulated in colon cancer cell lines, while inhibition of NF-κB reversed functions of lncRNA CASC2 and magnified roles of miR-19a. Our findings showed that lncRNA CASC2 inhibited cell viability in colon cancer cell lines and miR-19a reversed its functions through the NF-κB signalling pathway, suggesting that these could be factors in treating colon cancer in the future.

Momordin Ic induces G0/1 phase arrest and apoptosis in colon cancer cells by suppressing SENP1/c-MYC signaling pathway

Momordin Ic (MI) is a natural pentacyclic triterpenoid enriched in various Chinese natural medicines such as the fruit of Kochia scoparia (L.) Schrad. Studies have shown that MI presents antitumor properties in liver and prostate cancers. However, the activity and potential mechanisms of MI against colorectal cancer remain elusive. Here, we showed that MI inhibited cell proliferation with G0/1 phase cell cycle arrest in colon cancer cells. Moreover, it was observed that MI increased apoptosis compared to untreated cells. Further investigation showed that the SUMOylation of c-Myc was enhanced by MI and led to the down-regulated protein level of c-Myc, which is involved in regulating cell proliferation and apoptosis. SENP1 has been demonstrated to be critical for the SUMOylation of c-Myc. Meanwhile, knockdown of SENP1 by siRNA abolished the effects of MI on c-Myc level and cell viability in colon cancer cells. Together, these results revealed that MI exerted an anti-tumor activity in colon cancer cells via SENP1/c-Myc signaling pathway. These finding provide an insight into the potential of MI for colon cancer therapy.

Long noncoding RNA LINC01296 plays an oncogenic role in colorectal cancer by suppressing p15 expression.

ObjectiveTo examine the role of the long noncoding RNA LINC01296 in colorectal carcinoma (CRC) and to explore the underlying mechanism.MethodsWe detected LINC01296 expression levels in a cohort of 51 paired CRC and normal tissues. We also assessed the effects of LINC01296 on cell proliferation and apoptosis in CRC cells in vitro, and measured its effect on tumor growth in an in vivo mouse model. We identified the potential downstream targets of LINC01296 and assessed its regulatory effects.ResultsExpression levels of LINC01296 were elevated in 37/51 CRC tissues compared with the corresponding normal tissues and were significantly associated with tumor stage, lymph node metastasis, and distant metastasis. Knockdown of LINC01296 using antisense oligonucleotides inhibited cell proliferation and promoted apoptosis of colon cancer cells in vitro and inhibited tumor growth in vivo. Knockdown of LINC01296 also significantly increased the gene expression of p15 in colon cancer cells. LINC01296-specific suppression of p15 was validated by the interaction between enhancer of zeste homolog 2 and LINC01296.ConclusionOverexpression of LINC01296 suppressed the expression of p15 leading to CRC carcinogenesis. These findings may provide the basis for novel future CRC-targeted therapies.

Integrated analysis of potential pathways by which aloe-emodin induces the apoptosis of colon cancer cells

BackgroundColon cancer is a malignant gastrointestinal tumour with high incidence, mortality and metastasis rates worldwide. Aloe-emodin is a monomer compound derived from hydroxyanthraquinone. Aloe-emodin produces a wide range of antitumour effects and is produced by rhubarb, aloe and other herbs. However, the mechanism by which aloe-emodin influences colon cancer is still unclear. We hope these findings will lead to the development of a new therapeutic strategy for the treatment of colon cancer in the clinic.MethodsWe identified the overlapping targets of aloe-emodin and colon cancer and performed protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. In addition, we selected apoptosis pathways for experimental verification with cell viability, cell proliferation, caspase-3 activity, DAPI staining, cell cycle and western blotting analyses to evaluate the apoptotic effect of aloe-emodin on colon cancer cells.ResultsThe MTT assay and cell colony formation assay showed that aloe-emodin inhibited cell proliferation. DAPI staining confirmed that aloe-emodin induced apoptosis. Aloe-emodin upregulated the protein level of Bax and decreased the expression of Bcl-2, which activates caspase-3 and caspase-9. Furthermore, the protein expression level of cytochrome C increased in a time-dependent manner in the cytoplasm but decreased in a time-dependent manner in the mitochondria.ConclusionThese results indicate that aloe-emodin may induce the apoptosis of human colon cancer cells through mitochondria-related pathways.

Sesquiterpene lactone Bigelovin induces apoptosis of colon cancer cells through inducing IKK-β degradation and suppressing nuclear factor kappa B activation.

Bigelovin, a sesquiterpene lactone extracted from plant Inula helianthus aquatica, exhibited multiple interesting biological activities, including anti-inflammation, antiangiogenesis and cytotoxic action against cancer cells. In the present study, we found that Bigelovin reduced the viability of human colon cancer cells and induced their apoptosis in a time- and dose-dependent manner, with an IC50-5 μM. RNAseq and luciferase reporter analyses revealed that the nuclear factor kappa B (NF-κB) signaling was one of the most significantly inhibited pathways after Bigelovin treatment. Further systemic examination showed that exposure to Bigelovin resulted in ubiquitination and degradation of inhibitor of kappa-B kinase-beta (IKK-β) and decrease of IκB-α and p65 phosphorylation, which led to the downregulation of NF-κB-regulated genes expression. Moreover, enforced expression of exogenous IKK-β attenuated Bigelovin-induced NF-κB suppression and cell viability reduction. These results indicated that Bigelovin exerts a cytotoxic action against colon cancer cells through the induction of IKK-β degradation and consequently the inhibition of NF-κB signaling. Given the abnormal activation of NF-κB signaling in colorectal cancer (CRC) cells and the critical role of chronic inflammation in CRC development, it is conceivable that at least some colorectal cancer cells are addictive to NF-κB activation and targeting the pathway is an effective anti-CRC strategy.

Circ_0055625 knockdown inhibits tumorigenesis and improves radiosensitivity by regulating miR-338-3p/MSI1 axis in colon cancer

BackgroundRadiotherapy is a main therapeutic method for cancers, including colon cancer. In the current study, we aim to explore the effects of circular RNA (circRNA) circ_0055625 in the progression and radiosensitivity of colon cancer and the underlying mechanism.MethodsThe expression of circ_0055625 and musashi homolog 1 (MSI1) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). MSI1 protein expression was determined by Western blot. Cell proliferation was assessed by cell counting kit-8 (CCK-8) and colony formation assays. Cell survival fraction, apoptosis, and invasion were investigated by colony formation assay, flow cytometry analysis, and transwell invasion assay, respectively. Cell migration was detected by wound-healing and transwell migration assays. The binding relationship between microRNA-338-3p (miR-338-3p) and circ_0055625 or MSI1 was predicted by online databases and identified by Dual-Luciferase Reporter Assay. The effects of circ_0055625 silencing on the tumor formation and radiosensitivity of colon cancer in vivo were explored by in vivo tumor formation assay.ResultsCirc_0055625 and MSI1 were upregulated in colon cancer tissues and cells relative to control groups. Radiation treatment apparently increased the expression of circ_0055625 and MSI1 in colon cancer cells. Circ_0055625 knockdown or MSI1 silencing repressed cell proliferation, migration, and invasion and promoted cell apoptosis and radiosensitivity in colon cancer. Also, circ_0055625 silencing-mediated effects were attenuated by MSI1 overexpression. Additionally, circ_0055625 silencing reduced MSI1 expression, which could be attenuated by miR-338-3p inhibitor. Mechanically, circ_0055625 acted as a sponge for miR-338-3p to regulate MSI1. Furthermore, circ_0055625 knockdown hindered tumor growth and improved radiosensitivity in vivo.ConclusionCirc_0055625 repression inhibited the progression and radioresistance of colon cancer by downregulating MSI1 through sponging miR-338-3p. This result might provide a theoretical basis for improving the therapy of colon cancer with radiation.

Dietary Phytochemicals in Cancer Signalling Pathways: Role of miRNA Targeting.

Cancer is a multi-factorial health condition involving uncontrolled cell divisions. The disease has its roots in genetic mutation. This disease affects men, women, and even children. Chemotherapy, photodynamic, photothermal, and hormonal therapies have been used to treat this deadliest disease, but a huge percentage of patients have chances of disease recurrence or resistance. Nowadays, dysregulation in miRNAs is considered one of the key factors for the development and progression of different types of cancers as they control the expression of genes responsible for cell proliferation, growth, differentiation, and apoptosis. Dietary phytochemicals with anticancer properties have been gaining focus for cancer treatment since they have been found more effective in targeting cancer via regulating miRNAs expression. These phytochemicals have no side effects and are readily available at a low cost. Several dietary phytochemicals with regulatory effects on the expression of miRNAs have been reported, including curcumin, diallyl disulfide, 3, 30-diindolylmethane, ellagic acid, genistein, indole-3-carbinol, quercetin, resveratrol, and sulforaphane. They exert their regulatory effects against different cancers either by upregulating or downregulating different cancer signalling pathways and inhibiting their progression. Curcumin down-regulates SHH pathways, epigallocatechin-3-gallate regulates the Notch pathway and inhibits TGFβ1/SMAD signalling, and resveratrol regulates the Wnt/β-catenin pathway and carnosic acid-induced apoptosis in colon cancer cell via JAK2/STAT3 signalling pathway. The miRNAs are used for the treatment of cancer as essential modulators in cellular pathways. Therefore, identifying the miRNAs and their targets and countering them with specific phytochemicals provide a safe and effective mechanism for the treatment of cancer.

Gallic acid suppresses colon cancer proliferation by inhibiting SRC and EGFR phosphorylation.

The aim of the present study was to investigate the effects of gallic acid (GA) on the proliferation and apoptosis of colon cancer cells and to further clarify the mechanism of GA function associated with SRC and EGFR phosphorylation. HCT116 and HT29 cells were treated with different concentrations of GA for 24 h. Cell proliferation and apoptosis were analyzed using plate clone formation and flow cytometry assays, respectively. In addition, the expression of apoptosis-related proteins was examined by western blotting. Furthermore, the level of STAT3, AKT, SRC and EGFR phosphorylation was analyzed by western blotting and immunofluorescence. Subsequently, the SRC inhibitor PP2 and the EGFR inhibitor gefitinib were used to analyze the GA-associated mechanisms. In addition, a xenograft tumor model was established to confirm the effects of GA in vivo. The results indicated that GA inhibited cell proliferation and promoted cell apoptosis by upregulating the ratio of cleaved caspase-3/pro-caspase-3 and cleaved caspase-9/pro-caspase-9. Concurrently, GA decreased the level of phosphorylated (p)-SRC, p-EGFR, p-AKT and p-STAT3. Following treatment with PP2 and gefitinib in both cancer cell lines and animal model, GA was demonstrated to inhibit EGFR and SRC phosphorylation to downregulate STAT3 and AKT phosphorylation. In vivo, GA prevented tumor growth, promoted tumor apoptosis and decreased the level of p-SRC, p-EGFR, p-STAT3 and p-AKT. In conclusion, GA was indicated to suppress colon cancer proliferation by inhibiting SRC and EGFR phosphorylation.

Transcriptomic analysis reveals that combinations of vitamins A, D2, and D3 have synergistic effects in HCT-116 colon cancer cells by altering the expression of genes involved in multiple canonical pathways including apoptosis, regulation of the...

Integrated systems biology approaches suggest that combinations of nutrients may be more effective against cancer due to the large number of signaling pathways associated with cancer initiation and promotion. In a previous work, we have reported that combinations of vitamins A (as all trans-retinoic acid, ATRA), D2, and D3 act synergistically to induce apoptosis in colon and gastric cancer cells. In this work, we use whole-genome transcriptomic profiling to detect gene expression changes using RNA-seq to more comprehensively investigate the biological pathways affected by the combination of vitamin D2, D3 and ATRA. HCT-116 colon cancer cells were harvested, RNA was isolated and RNA-seq libraries were prepared using a Universal Plus mRNASeq kit. Sequencing was carried out on NovaSeq 6000. General quality-control metrics were obtained using FastQC and raw reads were aligned to human reference genome hg38 using STAR and BWA MEM. ENSEMBL genes were quantified using FeatureCounts, and differential expression statistics were computed using EdgeR. Specific gene expression was validated using qPCR. Transcriptomic analysis showed that of 26,313 genes analyzed, the expression of 8,402 genes was significantly altered (4030 up-regulated and 4373 down-regulated, FDR&lt;0.05) in the treated cells, of which, 3,621 genes were differentially expressed (fold change &lt;-1 or &gt;+1 and an FDR &lt;0.05). IngenuityÒ Pathway analysis revealed the involvement of 97 canonical pathways, with the top pathways including: mechanisms of cancer, apoptosis, myc-mediated apoptosis, regulation of the epithelial mesenchymal transition, and immunity. Keywords: apoptosis, cholcalciferol, colon cancer, caspase, CRMP1, ergocalciferol, IL-12, NOTCH1, RNA-seq, SMAD7, synergism, transcriptome

Identification of GSPT1 as prognostic biomarker and promoter of malignant colon cancer cell phenotypes via the GSK-3β/CyclinD1 pathway

Colon cancer is the third most common malignant tumor and its mortality rate ranks fourth among all malignant tumor types. Bioinformatics analysis has shown that GSPT1 is dysregulated in colon cancer and is associated with tumor progression. However, the underlying mechanism remains unclear. To address this research gap, we examined the impact of GSPT1 on cell proliferation, apoptosis, migration, and invasion in vitro as well as tumor growth in vivo in colon cancer by using a Cell Counting Kit-8 assay, flow cytometry, transwell migration assay, transwell invasion assay, and tumor xenograft model-based analysis, respectively. GSPT1 was significantly up-regulated in colon cancer tissues and cell lines. High GSPT1 expression was correlated with a larger tumor size. Depletion of GSPT1 suppressed cell proliferation, migration, and invasion-induced colon cancer cell apoptosis in vitro and restrained tumorigenicity in vivo in HCT116 colon cancer cells. Taken together, our findings suggest that the GSPT1/GSK pathway exerts tumor-promoting actions in colon cancer oncogenesis and progression. The GSPT1/GSK pathway may thus be an effective target for controlling colon cancer.

Pseudouridylate Synthase 7 Promotes Cell Proliferation and Invasion in Colon Cancer Through Activating PI3K/AKT/mTOR Signaling Pathway.

Colorectal cancer is commonly malignant tumor. Herein, we demonstrate that pseudouridylate synthase 7 (PUS7) is closely related to colon cancer. But the biological role of PUS7 in colon cancer is not known. The present study aims to investigate the effects of PUS7 in colon cancer clinical samples and cells and the related molecular mechanism. A profile data set was downloaded from the Cancer Genome Atlas database, which included data from colon cancer tissue samples and normal tissue samples. The top 200 differentially expressed genes were subsequently investigated by a protein-protein interaction (PPI) network. RT-PCR and western blot assays were used to determine gene expression levels. CCK8 assay, colony formation experiment, transwell and flow cytometry assay were used to determine cell viability, proliferation, invasion, and apoptosis, respectively. PUS7 is a key gene from the most significant module of the PPI network. PUS7 was upregulated in colon cancer tissues and cell lines. Moreover, PUS7 overexpression is significantly related to the poor survival rate for 60 colon cancer's patients. Cell proliferation and invasion was significantly reduced by PUS7 inhibition and promoted by PUS7 overexpression. The protein levels of cleaved caspase-3/9, c-myc, E-cadherin and vimentin genes were significantly regulated in colon cancer cells transfected with PUS7 interference or overexpression. PUS7 overexpression significantly upregulated the phosphorylation levels of PI3K, AKT and mTOR. The results of this study demonstrate thatPUS7 overexpression upregulates cell proliferation, invasion and inhibits cell apoptosis of colon cancer cells via activating PI3K/AKT/mTOR signaling pathway.

Vinpocetine inhibits the proliferation and induces apoptosis in human colon cancer cells

Vinpocetine induces anti-inflammatory effects in various inflammatory diseases via the inhibition of phosphodiesterase type-1-independent nuclear factor-κB signaling pathway and the release of inflammatory cytokines. In this study, we investigated the effect of vinpocetine on the proliferation of colon cancer cells and its underlying molecular mechanisms. Our data showed that vinpocetine inhibits the viability and proliferation of colon cancer cells. Vinpocetine treatment induced cell death in HCT116 cells, which the percentages of sub-G1 phase were significantly increased, and the apoptosis-related genes were regulated after HCT116 cells were treated with vinpocetine. In sum, our findings indicated that vinpocetine could be a therapeutically useful candidate in the treatment of colon cancer.

β‑asarone suppresses HCT116 colon cancer cell proliferation and liver metastasis in part by activating the innate immune system

Studies have revealed that β-asarone exerts a powerful inhibitory effect on the proliferation of human cancer cells. The authors' previous study demonstrated that β-asarone could induce LoVo colon cancer cell apoptosis in vitro and in vivo, indicating its anticancer properties. The present study aimed to determine the antineoplastic effect of β-asarone in HCT116 colon cancer cells. An in vitro proliferation assay using a real time cell analyzer demonstrated that β-asarone effectively decreased HCT116 cell proliferation in a dose-dependent manner. Bioinformatics analysis revealed that differentially expressed genes following β-asarone inhibition were involved in the ‘cell cycle’, ‘cell division’, ‘cell proliferation’ and ‘apoptosis’. Subsequently, a xenograft assay evidenced the inhibitory effect of β-asarone on the growth of HCT116 tumors in vivo. Further detection of immune-associated cytokines and cells suggested that β-asarone might be involved in the antitumor immune response by stimulating granulocyte-colony stimulating factor and increasing the number of macrophage cells in the spleen. Additionally, a murine model of splenic-transplantation verified the strong suppressive role of β-asarone in colon cancer liver metastasis in vivo. Taken together, the results of the current study revealed that β-asarone decreased HCT116 colon cancer cell proliferation and liver metastasis potentially by activating the innate immune system, supporting the multi-system regulation theory and providing a basis for further mechanistic studies on colon cancer.

Effect of rs67085638 in long non‐coding RNA (CCAT1) on colon cancer chemoresistance to paclitaxel through modulating the microRNA‐24‐3p and FSCN1

It has been reported that rs67085638 in long non‐coding RNAs (lncRNA)‐CCAT1 was associated with the risk of tumorigenesis. Also, CCAT1 could affect chemoresistance of cancer cells to paclitaxel (PTX) via regulating miR‐24‐3p and FSCN1 expression. In this study, we aimed to investigate the effect of rs67085638 on the expression of CCAT1/miR‐24‐3p/FSCN1 and the response of colon cancer to the treatment of PTX. 48 colon cancer patients were recruited and grouped by their genotypes of rs67085638 polymorphism as a CC group (N = 28) and a CT group (N = 20). PCR analysis, IHC assay and Western blot, TUNEL assay and flow cytometry were conducted. LncRNA‐CCAT1 and FSCN1 mRNA/protein were overexpressed, whereas miR‐24‐3p was down‐regulated in the CT‐genotyped patients and cells compared with those in the CC‐genotyped patients and cells. The survival of colon cancer cells was decreased, whereas the apoptosis of colon cancer cells was increased by PTX treatment in a dose‐dependent manner. MiR‐24‐3p was validated to target lncRNA‐CCAT1 and FSCN1 mRNA, and the overexpression of CCAT1 could reduce the expression of miR‐24‐3p although elevating the expression of FSCN1. Knockdown of lncRNA‐CCAT1 partly reversed the suppressed growth of CT‐genotyped tumours. And the knockdown of lncRNA‐CCAT1 partly reversed the dysregulation of lncRNA‐CCAT1 and FSCN1 mRNA/protein in rs67085638‐CT + NC shRNA mice. The findings of this study demonstrated that the presence of the minor allele of rs67085638 increased the expression of CCAT1 and accordingly enhanced the resistance to PTX. Down‐regulation of CCAT1 significantly re‐stored the sensitivity to PTX of colon cancer cells.

Licochalcone A inhibits proliferation and promotes apoptosis of colon cancer cell by targeting programmed cell death-ligand 1 via the NF-κB and Ras/Raf/MEK pathways

Ethnopharmacological relevanceGlycyrrhiza glabra L., a traditional medicinal, has a history of thousands of years. It is widely used in clinic and has been listed in Chinese Pharmacopoeia. Licochalcone A is a phenolic chalcone compound and a characteristic chalcone of Glycyrrhiza glabra L. It has many pharmacological activities, such as anti-cancer, anti-inflammatory, anti-viral and anti-angiogenic activities. Aim of the studyIn this study, we explored the anti-tumor activity and potential mechanism of licochalcone A in vitro and in vivo. Materials and methodsIn vitro, the mechanism of licochalcone A at inhibiting PD-L1 expression was investigated by molecular docking, western blotting, RT-PCR, flow cytometry, immunofluorescence and immunoprecipitation assays. The co-culture model of T cells and tumor cells was used to detect the activity of cytotoxic T lymphocytes. Colony formation, EdU labelling and apoptosis assays were used to detect changes in cellular proliferation and apoptosis. In vivo, anti-tumor activity of licochalcone A was assessed in a xenograft model of HCT116 cells. ResultsIn the present study, we found that licochalcone A suppressed the expression of programmed cell death ligand-1 (PD-L1), which plays a key role in regulating the immune response. In addition, licochalcone A inhibited the expressions of p65 and Ras. Immunoprecipitation experiment showed that licochalcone A suppressed the expression of PD-L1 by blocking the interaction between p65 and Ras. In the co-culture model of T cells and tumor cells, licochalcone A pretreatment enhanced the activity of cytotoxic T lymphocytes and restored the ability to kill tumor cells. In addition, we showed that licochalcone A inhibited cell proliferation and promoted cell apoptosis by targeting PD-L1. In vivo xenograft assay confirmed that licochalcone A inhibited the growth of tumor xenografts. ConclusionIn general, these results reveal the previously unknown properties of licochalcone A and provide new insights into the anticancer mechanism of this compound.

Musa balbisiana and Musa paradisiaca Starches Increase SCFA and Caspase-3 as well as Decrease β-glucuronidase and MDA of Mouse Model for Colon Cancer

BACKGROUND: Administration of resistant starch (RS) influences the diversity and the composition of microbiota as well as inhibits the growth of cancer cell. Banana as a potential source of RS has been reported. Although Musa paradisiaca has been reported to induce apoptosis in colon cancer cells, Musa balbisiana, which has low glycemic index and suitable for particular patients, has not been investigated yet.METHODS: Starches of M. balbisiana and M. paradisiaca were prepared and mixed with other components to make 3 types of mouse pellets. Mouse model for colon cancer was prepared and fed with different types of mouse pellets. Blood was collected and processed for measuring β-glucuronidase and malondialdehyde (MDA) with Enzyme-linked Immunosorbent Assay (ELISA) method. Resected ceca were incised to collect the inner part for short-chain fatty acid (SCFA) measurement with gas chromatography analysis. Resected colas were fixed and processed for immunohistochemistry to detect Caspase-3.RESULTS: Colon-cancer-mice fed with the M. balbisiana and M. paradisiaca starches-contained pellets had significant higher concentrations of total SCFA (p=0.003), acetic acid (p=0.000), propionic acid (p=0.000) and butyric acid (p=0.000); lower concentration of β-glucuronidase (p&lt;0.001); higher Caspase-3 score (p=0.040); and lower MDA concentration (p&lt;0.001) than colon-cancer-mice fed with standard pellet (control).CONCLUSION: M. balbisiana and M. paradisiaca starches could be suggested as potential anti-colon cancer RS. Further research should be carried out to disclose the starches mechanisms in colon cancer cell.KEYWORDS: Musa balbisiana, Musa paradisiaca, colon cancer, resistant starch, Caspase-3, SCFA, β-glucuronidase, malondialdehyde

Albumin-stabilized layered double hydroxide nanoparticles synergized combination chemotherapy for colorectal cancer treatment

Combination chemotherapy with two or more complimentary drugs has been widely used for clinical cancer treatment. However, the efficacy and side effects of combination chemotherapy still remain a challenge. Here, we constructed an albumin-stabilized layered double hydroxide nanoparticle (BLDH) system to simultaneously load and deliver two widely used anti-tumor drugs, i.e. 5-fluorouracil (5FU) and albumin-bound PTX (Abraxane, ABX) for colorectal cancer treatment. The cellular uptake test has revealed that 5FU-ABX encapsulated BLDH (BLDH/5FU-ABX) nanoparticles were efficiently internalized by the colorectal cancer cell (HCT-116), synergistically inducing apoptosis of colon cancer cells. The in vivo test has demonstrated that BLDH/5FU-ABX nanomedicine significantly inhibited the tumor growth after three intravenous injections, without any detectable side effects. The enhanced therapeutic effectiveness is attributed to efficient accumulation of BLDH/5FU-ABX at tumor sites and acid-sensitive release of co-loaded drugs. Thus, combination chemotherapy based on BLDH/5FU-ABX nanomedicine would be a new strategy for colorectal cancer treatment.

Over-Expression of MicroRNA-122 Inhibits Proliferation and Induces Apoptosis in Colon Cancer Cells.

MicroRNA, a non-coding RNA molecule plays a vital role in post transcriptional gene expression. MicroRNA-122, a liver specific microRNA was found to be downregulated in liver cancer and is associated with hepatocarcinogenesis. Being confirmed as tumor suppressor microRNA in liver carcinogenesis, we aimed to study the expression of microRNA-122 in colon cancer cell lines and the role of microRNA-122 in cell proliferation, invasion and migration of colon cancer cells. The expression of microRNA-122 is quantified using qRT-PCR by TaqMan universal primers. Colon cancer cell lines (SW480, SW620, HCT116) were transfected with microRNA-122 mimic and further studied for determining cell proliferation using CCK-8 kit, migration using Scratch assay, invasion using Transwell assay, apoptosis using Annexin-V FITC kit, and also gene expression. Gene expression results displayed decreased expression of microRNA-122 in colon cancer cell lines. Transfection with microRNA-122 mimics impaired the cell proliferation and migration compared with control. FACS analysis confirmed that the percentage of microRNA-122 mimic transfected cells undergoing early apoptosis was increased. Gene expression of AEG-1, PI3K, CDK6, and PCNA were found to be downregulated in microRNA-122 overexpressed cells. Migratory and invasion potential of transfected cells was lessened in mimic transfected cells compared to control. The overexpression of microRNA-122 inhibited the cellular proliferation, migration, invasion and increased percentage of cells undergoing early apoptosis, suggesting its anti-cancer potential. Studying the role of microRNA-122 and its interactions with oncogenes might pave the way to understand the underlying mechanism in colon cancer.