Migration Of HT-29 Cells Research Articles

Polyphyllin II Induces Apoptosis in Fibrosarcoma Cells via Activating Pyruvate Kinase M2.

Aerobic glycolysis is a metabolic reprogramming of tumor cells that is essential for sustaining their phenotype of fast multiplication by continuously supplying energy and mass. Pyruvate kinase M2 (PKM2) has a vital role in this process, which has given it high interest as a target for anticancer drug development. With potent toxicity to many types of cancer cells, polyphyllin II (PP2), a steroidal saponin isolated from the herbaceous plant Rhizoma paridis, brought to our attention that it might interfere with the PKM2 activity. In this study, we discovered that PP2 was a novel agonist of PKM2. PP2 activated recombinant PKM2 and changed the protein's oligomeric state to activate intracellular PKM2. At the same time, PP2 suppressed its protein kinase function by decreasing the content of nuclear PKM2. The mRNA levels of its downstream genes, such as Glut1, LDHA, and MYC, were inhibited. In addition, PP2 induced oxidative stress by downregulating the expression and activity of antioxidant proteins such as NQO1, TrxR, and Trx in HT-1080 cells, which in turn led to mitochondrial dysfunction and ultimately induced apoptosis. Moreover, PP2 reduced the proliferation and migration of HT-1080 cells. Thus, targeting the glycolysis pathway offers an unprecedented mode of action for comprehending PP2's pharmacological impacts and advances PP2's further development in fibrosarcoma therapy.

Targeting colorectal cancer with Herba Patriniae and Coix seed: Network pharmacology, molecular docking, and in vitro validation

BACKGROUND Herba Patriniae and Coix seed (HC) constitute a widely utilized drug combination in the clinical management of colorectal cancer (CRC) that is known for its diuretic, anti-inflammatory, and swelling-reducing properties. Although its efficacy has been demonstrated in a clinical setting, the active compounds and their mechanisms of action in CRC treatment remain to be fully elucidated. AIM To identify the active, CRC-targeting components of HC and to elucidate the mechanisms of action involved. METHODS Active HC components were identified and screened using databases. Targets for each component were predicted. CRC-related targets were obtained from human gene databases. Interaction targets between HC and CRC were identified. A “drug-ingredient-target” network was created to identify the core components and targets involved. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to elucidate the key pathways involved. Molecular docking between core targets and key components was executed. In vitro experiments validated core monomers. RESULTS Nineteen active components of HC were identified, with acacetin as the primary active compound. The predictive analysis identified 454 targets of the active compounds in HC. Intersection mapping with 2685 CRC-related targets yielded 171 intervention targets, including 30 core targets. GO and KEGG analyses indicated that HC may influence the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Molecular docking showed that acacetin exhibited an optimal interaction with AKT1 , identifying PI3K , AKT , and P53 as key genes likely targeted by HC during CRC treatment. Acacetin inhibited HT-29 cell proliferation and migration, as well as promoted apoptosis, in vitro . Western blotting analysis revealed increased p53 and cleaved caspase-3 expression and decreased levels of p-PI3K , p-Akt , and survivin, which likely contributed to CRC apoptosis. CONCLUSION Acacetin, the principal active compound in the HC pair, inhibited the proliferation and migration of HT-29 cells and promoted apoptosis through the PI3K/Akt/p53 signaling pathway.

Effects of photobiomodulation on colon cancer cell line HT29 according to mitochondria

Background/AimAlthough photobiomodulation therapy (PBMt) is available to alleviate post-operative side effects of malignant diseases, its application is still controversial due to some potential of cancer recurrence and occurrence of a secondary malignancy. We investigated effect of PBMt on mitochondrial function in HT29 colon cancer cells. MethodsHT29 cell proliferation was determined with MTT assay after PBMt. Immunofluorescent staining was performed to determine mitochondrial biogenesis and reactive oxygen species (ROS). Mitochondrial membrane potential was measured with Mitotracker. Western blotting was executed to determine expression of fission, fusion, UCP2, and cyclin B1 and D1 proteins. In vivo study was performed by subcutaneously inoculating cancer cells into nude mice and immunohistochemistry was done to determine expression of FIS1, MFN2, UCP2, and p-AKT. ResultsThe proliferation and migration of HT29 cells reached maximum with PBMt (670 nm, light emitting diode, LED) at 2.0 J/cm2 compared to control (P < 0.05) with more expression of cyclin B1 and cyclin D1 (P < 0.05). Immunofluorescent staining showed that ROS and mitochondrial membrane potential were enhanced after PBMt compared to control. ATP synthesis of mitochondria was also higher in the PBMt group than in the control (P < 0.05). Expression levels of fission and fusion proteins were significantly increased in the PBMt group than in the control (P < 0.05). Electron microscopy revealed that the percentage of mitochondria showing fission was not significantly different between the two groups. Oncometabolites including D-2-hydoxyglutamate in the supernatant of cell culture were higher in the PBMt group than in the control with increased UCP2 expression (P < 0.05). Both tumor size and weight of xenograft in nude mice model were bigger and heavier in the PBMt group than in the control (P < 0.05). Immunohistologically, mitochondrial biogenesis proteins UCP2 and p-AKT in xenograft of nude mice were expressed more in the PBMt group than in the control (P < 0.05). ConclusionsTreatment with PBM using red light LED may induce proliferation and progression of HT29 cancer cells by increasing mitochondrial activity and fission.

Synergic effects and possible mechanism of emodin and stilbene glycosides on colorectal cancer

BackgroundPolygonum multiflorum (PM) is a core herb that enhances immunity. It can also detoxify, reduce swelling, and intercept malaria. Its main components, emodin (EMD) and 2,3,5,4'-Tetrahydroxy stilbene-2-O-β-D-glucoside (stilbene glycoside, TSG), have good anti-cancer potential. PurposeThe study aims to investigate synergic effects of EMD and TSG on CRC and its possible mechanism. MethodsNetwork pharmacology and bioinformatics were used to identify targets. HPLC was used to analyze the effective ingredients in PM and to determine the content of the main ingredients. HT-29 cells were used for in vitro experiments. Cell Counting Kit-8 (CCK8) and scratch test were used to detect the effects of various chemical components of PM on the proliferation and migration of HT-29 cells, and Western Bolt (WB) test was used to evaluate the effects of EMD and TSG on P53 pathway. In vivo experiments, the effects of EMD and TSG were evaluated by measuring tumor weight and tumor volume in CRC mice model and histological analysis were carried out with HE staining. The expressions of HSP90, P53, COX2, and ROS were detected by quantitative reverse transcription polymerase chain reaction (PCR), and IL-1β, IL-4, IL-6, IL-10, TGF-β and IFN-γ were detected by enzyme linked immunosorbent assay (ELISA). WB and Immunohistochemistry (IHC) were used to detect the expression of P53 related proteins. ResultsNetwork pharmacology showed PM closely related to colorectal cancer pathway and the core targets included STAT3 and P53; bioinformatics indicated P53 played an important role in the development and prognosis of CRC; chemical analysis showed identified and quantified gallic acid (GA), cis-TSG, trans-TSG, Emodin glucoside(EMDG), physcion glucoside (PHYG), EMD in PM; EMD induced apoptosis and TSG inhibited migration of HT-29 cells; EMD and TSG could coordinately shrink tumor size of CRC mice, elevate expressions of F4/80, decrease the content of IL-6 and TGF-β, promote tumor oxidized and reduce expression of P53 and STAT3 in the tumor. ConclusionsIn vitro experiments showed that TSG inhibited cancer cell migration and EMD induced apoptosis. EMD and TSG had synergic effects on CRC, whose possible mechanism might be to regulate the expression of cytokines and inhibit P53 pathway.

Abstract 6960: Lysosome inhibition suppress collective cell migration through caveolin-1 mediated E-cadherin stabilization in colon cancer cells

Abstract In tumor nest growth and collective cell migration, the dynamics of E-cadherin is critical, and been shown to be regulated by cell vesicle traffic system. Caveolin-1 is the vesicle protein to regulate caveolae associated endocytosis, many of the membrane receptors are shown been regulated by caveolin-1 in cancer progression, however, the role is still controversial. This study demonstrated the effect of lysosome inhibition in caveolin-1 mediated E-cadherin turnover in the cell cohort of colon cancer cells. HT-29 colon cancer cells were used in this study, the cells were treated with chloroquine to inhibit lysosome activity. The cell spheroid from HT-29 cells were also collected according to cell adhesion ability. Caveolin-1 and E-cadherin were immuno-stained and revealed by confocal microscopy. In the result of immunostaining, caveolin-1 was showed the co-localization with E-cadherin at cell-cell contacts. When cells were treated with chloroquine, the lysosome inhibitor, the collective cell migration of HT-29 cells were suppressed, and stable caveolin-1 distribution was found accumulated on the cell-cell contacts., meanwhile, chloroquine has no effect on clathrin distribution at either cell-cell contacts or cell leading edge. Furthermore, the distribution of caveolin-1 at cell-cell contacts on cell spheroid that derived from HT-29 cells was decreased. The results of these study suggested lysosome plays important role in mediating caveolin-1 regulated E-cadherin dynamics in collective cell migration, but not in the cell spheroid formation. The results of these study demonstrated chloroquine can be the potential inhibitor for collective cell migration in colon cancer cells through caveolin-1 mediated vesicle transport. Citation Format: Yu-Chien Ching, Hui-Chun Chen, Yu-Chun Wang, Chun-Pu Cheng, Chia-En Ku, Shin-Ru Lee, Wei-Ting Chao. Lysosome inhibition suppress collective cell migration through caveolin-1 mediated E-cadherin stabilization in colon cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6960.

GALNT12 promotes fibrosarcoma growth by accelerating YAP1 nuclear localization.

Fibrosarcoma is a highly malignant type of soft tissue sarcoma that currently lacks effective treatment options. Polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12) belongs to the uridine diphosphate N-acetylgalactosamine gene family, which is involved in numerous biological processes of diseases, such as tumor progression. Its upregulated expression is closely associated with the development of colorectal cancer. However, research on the role of GALNT12 in fibrosarcoma is currently limited. The present study aimed to assess the expression and biological function of GALNT12 in fibrosarcoma. Patient data and tissue samples were collected and public datasets were obtained from the Gene Expression Omnibus (GSE24369 and GSE21124). Immunofluorescence assays were performed to observe the cellular localization of GALNT12. GALNT12 expression was measured using reverse transcription-quantitative PCR, western blotting and immunohistochemistry. Small interfering RNAs were constructed to knock down GALNT12 expression in HT-1080 cells. Cell Counting Kit-8 and EdU assays were used to assess fibrosarcoma cell proliferation. Wound healing and Transwell assays were used to detect migration. Gene set enrichment analysis was performed to identify key pathways. Paired and unpaired Student's t-test, Fisher's exact test and one-way ANOVA (followed by Tukey's Honest Significant Difference test) were used to analyze the data. It was demonstrated that GALNT12 expression was upregulated in both fibrosarcoma cell lines and tissue samples and predicted poor patient prognosis. In vitro experiments demonstrated that high GALNT12 expression levels significantly increased HT-1080 cell proliferation and migration. Furthermore, it was demonstrated that high GALNT12 expression levels were closely associated with the yes1 associated transcriptional regulator (YAP1) signaling pathway. Knockdown of GALNT12 inhibited YAP1 nuclear translocation, which affected activation of key downstream genes including AMOTL2, BIRC5 and CYR61. Therefore, the present study demonstrated that GALNT12 promoted fibrosarcoma progression. GALNT12 could be a potential biomarker for this disease and may potentially provide new ideas for targeted therapy of fibrosarcoma in the future.

Proliferation, migration, and resistance to oxidative and thermal stresses of HT1080 cells with knocked out genes encoding Hsp90α and Hsp90β

Heat shock protein 90 (Hsp90) fulfils essential housekeeping functions in the cell associated with the folding, stabilization, and turnover of various proteins. In mammals, there exist two Hsp90 isoforms, stress-inducible Hsp90α and constitutively expressed Hsp90β. In an attempt to identify cellular processes dependent on Hsp90α and Hsp90β, we generated a panel of clones of human fibrosarcoma HT1080 cells with the knocked out HSP90AA1 or HSP90AB1 genes encoding, respectively, Hsp90α and Hsp90β. The knockout of the HSP90AA1 and HSP90AB1 genes practically did not affect cell proliferation and resistance to thermal shock and oxidative stress. The loss of Hsp90α in Hsp90α-null cell clones also did not impair cell migration, while the migration of the Hsp90β-null cell clones was prominently reduced as compared to parent HT1080 cells. This indicated the necessity of Hsp90β for efficient basal migration of HT1080 cells whereas Hsp90α seems to be dispensable for this process. The knockout of one Hsp90 isoform was invariably accompanied by an increase in the level of the other Hsp90 isoform by 30–50%, which partly or fully compensated for a decrease in the total level of Hsp90. Thus, we demonstrated the dispensability of Hsp90α and Hsp90β for HT1080 cells in several cellular processes under normal and stress conditions, which suggested the participation of the two Hsp90 isoforms in the same biological processes and full or at least partial functional substitution of one Hsp90 isoform by the other.

Identification and characterization of the CDK1-BMAL1-UHRF1 pathway driving tumor progression

The abnormal regulation of BMAL1 could lead to the occurrence and progression of various tumors. However, the mechanism of phosphorylation regulation of BMAL1 in tumorigenesis remains poorly understood. In this study, we report a previously unrecognized BMAL1 dephosphorylation pathway that promotes tumor progression. BMAL1 accelerates cell proliferation, migration, and invasion of HT1080 and Calu1 cells. CDK1 binds to BMAL1 through a conserved domain and regulates the dephosphorylation of BMAL1 on Ser42 residues, but not on Ser78 or Thr224, thereby enhancing the oncogenic activity of BMAL1. Dephosphorylation of BMAL1 Ser42 promotes tumor growth and metastasis in mouse subcutaneous transplantation tumor and lung metastatic tumor models. Moreover, UHRF1 is recognized as an important target gene of BMAL1 in cancer cells. Consequently, UHRF1 depletion mimics BMAL1 deficiency with respect to tumor suppression, whereas transfection-enforced re-expression of UHRF1 restores tumor growth in BMAL1-deficient cells. These findings suggest a link between the circadian clock regulator and cancer progression.

Mechanisms of Antitumor Invasion and Metastasis of the Marine Fungal Derivative Epi-Aszonalenin A in HT1080 Cells

Epi-aszonalenin A (EAA) is an alkaloid that is isolated and purified from the secondary metabolites of coral symbiotic fungi and has been shown to have good atherosclerotic intervention activity and anti-angiogenic activity in our previous studies. In the present study, antiangiogenic activity was used as a basis of an intensive study of its mechanism of action against tumor metastasis and invasion. Invasive metastatic pairs are a hallmark of malignancy, and the dissemination of tumor cells is the most dangerous process in the development of tumors. The results of cell wound healing and the Transwell chamber assay showed that EAA interfered well with PMA-induced migration and invasion of HT1080 cells. Western blot and the ELISA assay showed that EAA decreased MMPs and vascular endothelial growth factor (VEGF) activity and inhibited the expression of N-cadherin and hypoxia-inducible factor-1α (HIF-1α) by regulating the phosphorylation of downstream mitogen-activated protein kinase (MAPK), PI3K/AKT, and NF-κB pathways. Simultaneous molecular docking results revealed that the mimic coupling between the EAA and MMP-2/-9 molecules formed a stable interaction. The results of this study provide a research basis for the inhibition of tumor metastasis by EAA, and together with previous studies, confirm the potential pharmacology and drug potential for this class of compound for application in angiogenesis-related diseases and further improve the availability of coral symbiotic fungi.

Influence of Plasma-Isolated Anthocyanins and Their Metabolites on Cancer Cell Migration (HT-29 and Caco-2) In Vitro: Results of the ATTACH Study.

Cancer mortality is mainly due to metastasis. Therefore, searching for new therapeutic agents suppressing cancer cell migration is crucial. Data from human studies regarding effects of anthocyanins on cancer progression, however, are scarce and it is unclear whether physiological concentrations of anthocyanins and their metabolites reduce cancer cell migration in vivo. In addition, interactions with chemotherapeutics like 5-fluorouracil (5-FU) are largely unknown. Thus, we combined a placebo-controlled, double-blinded, cross-over study with in vitro migration studies of colon cancer cell lines to examine the anti-migratory effects of plasma-isolated anthocyanins and their metabolites (PAM). Healthy volunteers (n = 35) daily consumed 0.33 L of an anthocyanin-rich grape/bilberry juice and an anthocyanin-depleted placebo juice for 28 days. PAM were isolated before and after intervention by solid-phase extraction. HT-29 and Caco-2 cells were incubated with PAM in a Boyden chamber. Migration of HT-29 cells was significantly inhibited by PAM from juice but not from placebo. In contrast, Caco-2 migration was not affected. Co-incubation with 5-FU and pooled PAM from volunteers (n = 10), which most effectively inhibited HT-29 migration, further reduced HT-29 migration in comparison to 5-FU alone. Therefore, PAM at physiological concentrations impairs colon cancer cell migration and may support the effectiveness of chemotherapeutics.

Pentapeptide AYP from Isochrysis Zhanjiangensis Exhibits Antiangiogenic Activity in HT1080 Cells and HUVECs by Suppressing Migration and Invasion In Vitro.

Microalgae are important biological sources of marine active peptides and renewable biological resources. Isochrysis zhanjiangensis has been widely used in biological ultrafiltration membranes and aquaculture. However, there are relatively few studies on its component structure and diverse activities. In this study, the mechanism of action of previously isolated pentapeptides (AYP, Ala-Tyr-Ala-Pro-Glu) on inflammation and tumor angiogenesis was evaluated. The results showed that AYP could effectively inhibit the invasion and migration of human umbilical vein endothelial cells (HUVECs) and HT1080 cells by downregulating the expression of MMP-2/-9, independent of cytotoxicity. Especially after 100 μM AYP treatment, the ability to inhibit migration was about 67.7% ± 1.9 for HT1080 cells and 63.6% ± 1.3 for HUVECs, respectively. In addition, the activity of iNOS and COX-2 was decreased by inhibiting the oversecretion of VEGF in HT1080 cells induced by CoCl2 and the activation of VEGFR-2 in HUVECs and by regulating PI3K/AKT and Ras/MAPK signaling pathways. It can prevent inflammation and block tumor angiogenesis. Therefore, AYP is expected to become a drug or functional food to prevent and treat tumor angiogenesis.

Tumor-Inhibitory Effects of Zerumbone Against HT-29 Human Colorectal Cancer Cells.

Colorectal cancer (CRC) is the second cause of cancer-associated death globally. Recently, herbal medicinal products and, in particular, zerumbone have been widely studied and used for cancer treatment as they induce significant anti-cancer effects. However, there is limited information about the anti-cancer effects of zerumbone in CRC. Therefore, we aimed to investigate the in vitro anti-cancer effects of the zerumbone in CRC, focusing on cell apoptosis and migration. Anti-proliferative and anti-migratory effects of zerumbone on HT-29 cells were evaluated using MTT and scratch wound healing assay, respectively. Quantitative real-time PCR (qRT-PCR) was performed to determine the mRNA expression levels of migration and apoptosis-related genes. Apoptosis and cell cycle distribution were evaluated by flow cytometry. The intracellular level of reactive oxygen species (ROS) was measured using a ROS assay kit. Additionally, matrix metalloproteinase-2/-9 (MMP-2/-9) activity was determined using gelatin zymography. Zerumbone suppressed the viability of the HT-29 cells dose-dependently while having less cytotoxicity on normal NIH/3T3 cells. Zerumbone induced apoptosis in HT-29 cells and arrested the cell cycle in the G2/M phase. These effects were associated with alteration in the expression of apoptosis-related genes (up-regulation of Bax and down-regulation of Bcl-2 genes). Zerumbone also enhanced the generation of ROS in HT-29 cells. Furthermore, zerumbone significantly inhibited the migration of HT-29 cells and decreased MMP-2/-9 mRNA expression and activity. Our findings provide a potential use for zerumbone to induce apoptosis and suppress metastasis in HT-29 cells; thus, it could be developed as a promising natural agent for future CRC therapy.

DNA aptamer S11e recognizes fibrosarcoma and acts as a tumor suppressor

Fibrosarcoma is a serious malignant mesenchymal tumor with strong invasiveness, high recurrence, and poor prognosis. Currently, surgical resection is the main treatment for fibrosarcoma. However, due to the lack of specific biomarkers, the inability to accurately diagnose fibrosarcoma can lead to sub-optimal surgical outcomes and decreased survival. Here, we seek to address this translational barrier and we show that DNA aptamer S11e was able to recognize fibrosarcoma cells (HT1080) but not human embryonic lung fibroblast cells with Kd values in the nanomolar range. In addition, we found that S11e discerned tumors in HT1080 xenograft mouse models and tumor tissues from fibrosarcoma patients. Furthermore, we demonstrated that S11e internalized into HT1080 cells independent of the lysosome pathway and located in mitochondria. Moreover, we revealed that S11e promoted the apoptosis of HT1080 cells and inhibited HT1080 cell migration. Finally, we investigated the biologically functional cellular target of S11e using a mass spectrometry approach, and identified that Diablo/SMAC protein is a cellular binding protein of S11e, by interacting to which S11e inhibited HT1080 cell migration and invasion. Taken together, these results provide the evidence that S11e may be useful for early diagnosis, targeted therapy, and prognostication of fibrosarcoma.

Onion Peel Extract Inhibits Cancer Cell Growth and Progression through the Roles of L1CAM, NF-κB, and Angiogenesis in HT-29 Colorectal Cancer Cells.

Colorectal cancer (CRC) is an aggressive malignancy. Critical mechanisms that support CRC progression include cell migration, invasion, metastasis, and angiogenesis, which is associated with L1 cell adhesion molecule (L1CAM) and nuclear factor-kappa B (NF-κB) signaling pathways. In this study, viability of HT-29 cells and human umbilical vein endothelial cells (HUVECs) was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, and cell apoptosis was investigated by flow cytometry assays. HT-29 cell migration and invasion were observed by wound healing and Transwell invasion assays, respectively, and tube formation of HUVECs was observed by tubulogenesis assays. L1CAM and NF-κB protein expressions in HT-29 cells treated with onion peel extract were determined by indirect immunofluorescence. Results showed that high dose treatments of onion peel extract inhibited cell viability of both HT-29 cells and HUVECs, induced HT-29 cell apoptosis, and inhibited HT-29 cell migration and invasion. Moreover, onion peel extract decreased total HUVEC tube length and, at a concentration of 10 μg/mL, showed potential to downregulate L1CAM and NF-κB. In conclusion, onion peel extract inhibits HT-29 cell growth, migration, and invasion through suppressing pathways related to angiogenesis downstream of L1CAM-activated NF-κB.

Self-assembled fluorescent hybrid nanoparticles-mediated collaborative lncRNA CCAT1 silencing and curcumin delivery for synchronous colorectal cancer theranostics

BackgroundCancer synergistic therapy strategy in combination with therapeutic gene and small molecule drug offers the possibility to amplify anticancer efficiency. Colon cancer-associated transcript-1 (CCAT1) is a well identified oncogenic long noncoding RNA (lncRNA) exerting tumorigenic effects in a variety of cancers including colorectal cancer (CRC).ResultsIn the present work, curcumin (Cur) and small interfering RNA targeting lncRNA CCAT1(siCCAT1) were co-incorporated into polymeric hybrid nanoparticles (CSNP), which was constructed by self-assembling method with two amphiphilic copolymers, polyethyleneimine-poly (d, l-lactide) (PEI-PDLLA) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol) (DSPE-mPEG). Owing to the multicolor fluorescence characteristics of PEI-PDLLA, the constructed CSNP could be served as a theranostic nanomedicine for synchronous therapy and imaging both in vitro and in vivo. Resultantly, proliferation and migration of HT-29 cells were efficiently inhibited, and the highest apoptosis ratio was induced by CSNP with coordination patterns. Effective knockdown of lncRNA CCAT1 and concurrent regulation of relevant downstream genes could be observed. Furthermore, CSNP triggered conspicuous anti-tumor efficacy in the HT-29 subcutaneous xenografts model with good biosafety and biocompatibility during the treatment.ConclusionOn the whole, our studies demonstrated that the collaborative lncRNA CCAT1 silencing and Cur delivery based on CSNP might emerge as a preferable and promising strategy for synergetic anti-CRC therapy.Graphic abstract

Rhododendron molle G. Don Extract Induces Apoptosis and Inhibits Migration in Human Colorectal Cancer Cells and Potential Anticancer Components Analysis

Rhododendron molle G. Don is one example of traditional Chinese medicine with important medicinal value. In this study, the effects of methanol extract of R. molle leaves (RLE) on colorectal cancer HT-29 cells and its potential molecular mechanism were investigated. MTT analysis showed that RLE could significantly inhibit the cell viability and migration of HT-29 cells in a concentration-dependent manner. Cell cycle analyses via flow cytometer suggested that RLE induced DNA fragmentation, indicative of apoptosis, and arrest at the S phase in HT-29 cells. Quantitative real-time PCR (qRT-PCR) analysis showed that RLE could upregulate the mRNA expression of p53 and p21 in HT-29 cells, which would result in HT-29 cells being blocked in S phase. Meanwhile, RLE could upregulate the expression of Bax, and downregulate the expression of Bcl-2, which would induce cell apoptosis. Further western blot analysis showed that the protein expression changes of Bax and P53 were basically consistent with the results of qRT-PCR. In addition, GC-MS analysis detected 17 potential anticancer components in R. molle. These results indicate that R. molle has significant anticancer activity, which provides some useful information for further study and clinical application for R. molle.

Celastrol Inhibits Proliferation and Migration, and Promotes Apoptosis of Colon Cancer Cell HT29

We have examined the effects of celastrol on the proliferation, migration, and apoptosis of colon cancer HT29 cells and miR-133b as a possible mechanism of action. The HT-29 cells were incubated with celastrol at different concentrations (0, 2, 4 μmol/L) for 24 h. Cell counting kit-8, scratch wound, and flow cytometry assays were used to evaluate the effects of celastrol on the HT29 cells’ proliferation, migration, and apoptosis. The content of the miR-133b in the HT29 cells and human normal colorectal mucosa fetal human cells was measured by quantitative real-time polymerase chain reaction. After treatment with different concentrations of celastrol, the proliferation and migration of the HT29 cells were both significantly inhibited in a dose-dependent manner (P &lt; 0.05). Additionally, flow cytometry assay showed that celastrol induced the apoptosis of the HT29 cells in a dose-dependent manner. The miR-133b in the HT-29 cells was significantly lower than that in the fetal human cells. After treatment with celastrol, the miR-133b in the HT-29 cells was 3.78 times (2 μmol/L celastrol) and 4.59 times (4μmol/L celastrol) the content of untreated cells. Celastrol significantly inhibited the proliferation and migration, and promoted apoptosis of the colon cancer cells, which may be mediated by upregulation of the miR-133b. The expression of the miR-133b in the colon cancer cells was significantly inhibited.

Correction: MALAT1 is Associated with Poor Response to Oxaliplatin-based Chemotherapy in Colorectal Cancer Patients and Promotes Chemoresistance through EZH2

In the original version of this article (1), wrong images were used in Fig. 2F (invasion of si-NC–transfected HT29OxR cells), Fig. 4C (migration of HT29 cells), and Fig. 5G (si-EZH2–transfected SW620 cells). The error occurred when the authors arranged the images for these figures. The authors regret this error.

Nuclear factor-κB plays an important role in Tamarixetin-mediated inhibition of matrix metalloproteinase-9 expression

Flavonoids possess a broad spectrum of pharmacological properties, including anti-cancer, anti-oxidant and immunomodulatory activities. The current study explored the potential of some less-studied flavonoids in inhibiting Matrix Metalloproteinase-9 (MMP-9), a prominent biomarker, upregulated in a variety of cancers and known to promote migration and invasion of cancer cells. Amongst these, Tamarixetin, a naturally occurring flavonoid derivative of Quercetin, demonstrated significant dose-dependent inhibition of MMP-9 expression. Furthermore, a substantial inhibition of migration, invasion and clonogenic potential of HT1080 cells was also observed in the presence of Tamarixetin, which further suggests its role as a potential anti-cancer agent. It is noteworthy that Tamarixetin inhibits nuclear translocation as well the activity of nuclear factor kappa B (NFκB), both of which are functions essential for the activation of MMP-9 in promoting tumorigenesis. Additionally, the endogenous regulators of MMP-9 that tightly control its activity were also modulated by Tamarixetin, as evident from the 1.9 fold increase in the expression of Tissue Inhibitor of Metalloproteinase-1 (TIMP-1), with a concomitant 2.2 fold decrease in Matrix Metalloproteinase-14 (MMP-14) expression. The results obtained were further corroborated in three dimensional (3D) tumor models, which showed significant inhibition of MMP-9 activity as well as reduced invasive potential in the presence of Tamarixetin. Taken together, our observations demonstrate for the first time, the anti-invasive potential of Tamarixetin in cancer cells, indicating its possible use as a template for novel therapeutic applications.

Combination of Pycnogenol and Melatonin Reduce PC-3 and HT29 Cell Migration: Comparison to the Actions of Cisplatin

Combination of Pycnogenol and Melatonin Reduce PC-3 and HT29 Cell Migration: Comparison to the Actions of Cisplatin