Proliferation Of HCT116 Colon Cancer Cells Research Articles

An extract from the frass of swallowtail butterfly (Papilio machaon) larvae inhibits HCT116 colon cancer cell proliferation but not other cancer cell types

BackgroundThe frass of several herbivorous insect species has been utilised as natural medicines in Asia; however, the metabolite makeup and pharmaceutical activities of insect frass have yet to be investigated. Oligophagous Papilionidae insects utilise specific kinds of plants, and it has been suggested that the biochemicals from the plants may be metabolised by cytochrome P450 (CYP) in Papilionidae insects. In this study, we extracted the components of the frass of Papilio machaon larvae reared on Angelica keiskei, Oenanthe javanica or Foeniculum vulgare and examined the biological activity of each component. Then, we explored the expression of CYP genes in the midgut of P. machaon larvae and predicted the characteristics of their metabolic system.ResultsThe components that were extracted using hexane, chloroform or methanol were biochemically different between larval frass and the host plants on which the larvae had fed. Furthermore, a fraction obtained from the chloroform extract from frass of A. keiskei-fed larvae specifically inhibited the cell proliferation of the human colon cancer cell line HCT116, whereas fractions obtained from the chloroform extracts of O. javanica- or F. vulgare-fed larval frass did not affect HCT116 cell viability. The metabolites from the chloroform extract from frass of A. keiskei-fed larvae prevented cell proliferation and induced apoptosis in HCT116 cells. Next, we explored the metabolic enzyme candidates in A. keiskei-fed larvae by RNA-seq analysis. We found that the A. keiskei-fed larval midgut might have different characteristics from the O. javanica- or F. vulgare-fed larval metabolic systems, and we found that the CYP6B2 transcript was highly expressed in the A. keiskei-fed larval midgut.ConclusionsThese findings indicate that P. machaon metabolites might be useful as pharmaceutical agents against human colon cancer subtypes. Importantly, our findings show that it might be possible to use insect metabolic enzymes for the chemical structural conversion of plant-derived compounds with complex structures.

Identification and verification of the role of crucial genes through which methionine restriction inhibits the progression of colon cancer cells.

Studies have shown that methionine restriction (MR) can inhibit tumor progression, but its mechanism in colon cancer is unknown. Through DESeq2 and Edge analysis of the GSE72131 and GSE103602 datasets, 649 co-upregulated and 532 co-downregulated genes affected by MR were identified, respectively. Enrichment analysis showed that these genes were closely associated with tumor progression. Combined with the differentially expressed genes of colon cancer in The Cancer Genome Atlas database, MR affected 330 dysregulated genes in colon cancer. On this basis, a transcriptional regulatory and competing endogenous RNA network was established and F transcription factor 1 and microRNA 17-92a-1 Cluster Host Gene were identified as a key transcription factor and long non-coding RNA, respectively. In addition, four genes (FA Complementation Group I, Holliday Junction Recognition Protein, Karyopherin Subunit Alpha 2 and Kinesin Family Member 15) were identified by analyzing the relationship between dysregulated genes and overall survival. Finally, western blotting, reverse transcription-quantitative PCR, Transwell and other in vitro experiments verified that MR inhibits HCT116 colon cancer cell proliferation, metastasis and invasion, induces apoptosis and downregulates 6 hub genes. Collectively, the present study identified potential targets for MR to inhibit colon cancer progression and contributed to the clinical application of MR.

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.

S100A9 Is Involved in Fusobacterium nucleatum -Induced Proliferation and Migration of Colon Cancer HCT116 and SW480 Cells

S100A9 Is Involved in Fusobacterium nucleatum -Induced Proliferation and Migration of Colon Cancer HCT116 and SW480 Cells

Anticancer Activities and QSAR Study of Novel Agents with a Chemical Profile of Benzimidazolyl-Retrochalcone

The present pharmacochemical and modelling work focused on a benzimidazolyl-chalcone series. These previously synthesized compounds were evaluated in vitro for their anticancer activities against a panel of seven human cancer cell lines and normal fibroblasts. Among the new benzimidazole-supported chalcones, nine (9) compounds (compounds 1 - 4, 6 - 8 and compounds 10 and 11) showed promising anticancer activities with IC50s ranging from 0.83 to 2.58 μM. Compounds 2 and 6 with IC50s of 0.83 and 0.86 μM, respectively, were shown to be potent inhibitors of HCT-116 colon cancer cell proliferation. It was therefore necessary, for a development of this new series of chalcones, to establish through a QSAR study, their quantum descriptors according to the DFT calculation method and following the B3LYP/6-31+G (d,p) theory. These descriptive and predictive studies focused on the colon HCT 116 cell line which was found to be more sensitive to the anticancer action of our benzimidazolyl-retrochalcones. QSAR study showed that the electronic energy (Eelec), lipophilicity (logP), chemical softness (S) and chemical hardness (η) of benzimidazolyl-retrochalcones play an important role in inhibiting cancer cell proliferation.

Zerumbone reduces proliferation of HCT116 colon cancer cells by inhibition of TNF-alpha

Zerumbone is a known anti-cancer herbal compound. However, the actual protein target is not fully understood or known. This investigation focus on the association of zerumbone in HCT116 colon cancer cell proliferation and its link with TNF-alpha. The study shows that with the increasing concentration of zerumbone, there was a reduction of HCT116 cells proliferation based on the cell line study and hence higher TNF-alpha inhibition based on the TNF-alpha assay. The study also emphasizes on the computational aspect by investigating the molecular docking analysis of zerumbone against TNF-alpha. The docked complex was further validated using molecular dynamics simulation studies. The docking analysis observed that alpha-beta unsaturated carbonyl scaffold is an important moiety for the anti-cancer activity of zerumbone. Furthermore, the DFT analysis also confirms the reactivity nature of zerumbone based on the frontier molecular orbital analysis.

Role of endogenous and exogenous nitric oxide, carbon monoxide and hydrogen sulfide in HCT116 colon cancer cell proliferation

The role of the three gasotransmitter systems – nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) – in cancer cells has not yet been studied simultaneously in the same experimental system. We measured the expression of NO and CO and H2S generating enzymes in primary colon cancer tissues and HCT116 colon cancer cells, and evaluated the effect of their pharmacological inhibition or pharmacological donation on cell proliferation. Increased expression of iNOS, nNOS, HO-1, CBS and 3-MST was detected in colon cancer. Inhibitors of NOS, HO-1/2, CBS/CSE and 3-MST, at lower concentrations, slightly stimulated HCT116 cell proliferation, but inhibited proliferation at higher concentrations. Donors of NO, CO or H2S inhibited HCT116 proliferation in a concentration-dependent manner. Inhibition of the cGMP/VASP pathway, Akt and p44/42 MAPK (Erk1/2) inhibited HCT116 cell proliferation. Endogenous NO and H2S biosynthesis were found to play a role in the maintenance of the activity of the cGMP/VASP pathway in HCT116 cells. We conclude that each of the three gasotransmitters play similar, bell-shaped roles in the control of HCT116 cell proliferation: endogenously produced NO, CO and H2S, at an optimal concentration, support HCT116 proliferation; inhibition of their production (which decreases gasotransmitter levels below optimal concentrations) as well as exogenous delivery of these gasotransmitters (which increases gasotransmitter levels above optimal concentrations) suppresses colon cancer cell proliferation. The current data give a mechanistic explanation for the paradoxical finding that both inhibitors and donors of NO, CO and H2S exert anticancer actions in cancer cells.

In vitro targeting of colon cancer cells using spiropyrazoline oxindoles

We report on the synthesis and biological evaluation of a library of twenty-three spiropyrazoline oxindoles. The antiproliferative activity of the chemical library was evaluated in HCT-116 p53(+/+) human colon cancer cell line with eight derivatives displaying good activities (IC50<15 μM). To characterize the molecular mechanisms involved in compound antitumoral activity, two spiropyrazoline oxindoles were selected for further studies. Both compounds were able to induce apoptosis and cell cycle arrest at G0/G1 phase and upregulated p53 steady-state levels, while decreasing its main inhibitor MDM2. Importantly, cytotoxic effects induced by spiropyrazolines oxindoles occurred in cancer cells without eliciting cell death in non-malignant CCD-18Co human colon fibroblasts. Additionally, we demonstrated that the combination of spiropyrazoline oxindole 2e with sub-toxic concentrations of the chemotherapeutic agent 5-fluorouracil (5-FU) exerted a synergistic inhibitory effect on HCT-116 colon cancer cell proliferation. Collectively, our results show the potential of spiropyrazoline oxindoles for development of novel anticancer agents.

Ginsenoside Rh2 inhibiting HCT116 colon cancer cell proliferation through blocking PDZ-binding kinase/T-LAK cell-originated protein kinase

BackgroundGinsenoside Rh2 (GRh2) is the main bioactive component in American ginseng, a commonly used herb, and its antitumor activity had been studied in previous studies. PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), a serine/threonine protein kinase, is highly expressed in HCT116 colorectal cancer cells. MethodsWe examined the effect of GRh2 on HCT116 cells ex vivo. Next, we performed in vitro binding assay and in vitro kinase assay to search for the target of GRh2. Furthermore, we elucidated the underlying molecular mechanisms for the antitumor effect of GRh2 ex vivo and in vivo. ResultsThe results of our in vitro studies indicated that GRh2 can directly bind with PBK/TOPK and GRh2 also can directly inhibit PBK/TOPK activity. Ex vivo studies showed that GRh2 significantly induced cell death in HCT116 colorectal cancer cells. Further mechanistic study demonstrated that these compounds inhibited the phosphorylation levels of the extracellular regulated protein kinases 1/2 (ERK1/2) and (H3) in HCT116 colorectal cancer cells. In vivo studies showed GRh2 inhibited the growth of xenograft tumors of HCT116 cells and inhibited the phosphorylation levels of the extracellular regulated protein kinases 1/2 and histone H3. ConclusionThe results indicate that GRh2 exerts promising antitumor effect that is specific to human HCT116 colorectal cancer cells through inhibiting the activity of PBK/TOPK.

Inhibiting CD164 Expression in Colon Cancer Cell Line HCT116 Leads to Reduced Cancer Cell Proliferation, Mobility, and Metastasis in vitro and in vivo

Background: CD164 (Endolyn) is a sialomucin, which has been found to play roles in regulating proliferation, adhesion, and differentiation of hematopoietic stem cells. Possible association of CD164 with solid cancer development remains unknown.Methods and Results: We first studied CD164 expression in biopsies from colorectal cancer, breast, and ovary cancer patients by semi-quantitative immunohistochemistry, and found that CD164 was strongly expressed in all the colorectal cancer samples compared to the matching normal colon tissues. The possible roles of CD164 in colon cancer development were further investigated using a well-established human colon cancer cell line HCT116. We found that knockdown of CD164 expression in HCT116 cells significantly inhibited cell proliferation, mobility, and metastasis in vitro and in vivo. The knockdown of CD164 expression was associated with decreased chemokine receptor CXCR4 expression HCT116 cell surface and immunoprecipitation studies showed that CD164 formed complexes with CXCR4.Conclusions: CD164 is highly expressed in the colon cancer sites, and it promotes HCT116 colon cancer cell proliferation and metastasis both in vitro and in vivo, and the effects may act through regulating CXCR4 signaling pathway. Therefore, CD164 may be a new target for diagnosis and treatment for colon cancer.

Effect of Urtica dioica on proliferation of HCT-116 colon cancer cell line

Urtica dioica L. (stinging nettle), a member of the Urticaceae family is a plant which has been used as a remedy for diabetes mellitus (1), benign prostatic hyperplasia (2), arthritis (3), allergic rhinitis (4), hypertension and cardiovascular disease (5). In recent studies it was shown that extract of Urtica dioica exhibited significant growth reduction in human prostatic epithelial cells (6) and inhibition on adenosine deaminase activity in prostate tissue. In this study we aimed to investigate the effect of Urtica dioica on proliferation of HCT-116 colon cancer cell line. Herbal preparation of Urtica dioica was made by ethanol extraction which was followed by evaporation. HCT-116 cells were incubated with different doses of Urtica dioica ranging from 3,33mg/mL to 42,8mg/mL for 24 hours. Cell viability was measured with MTT test. Results showed that Urtica dioica (33,3mg/mL, 42,8mg/mL) inhibited HCT-116 colon cancer cell proliferation significantly (p<0,001). Further studies are needed to reveal the effectiveness of Urtica dioica as an alternative therapy for colon cancer.