scholarly journals Synergistic Effects of Simvastatin and Irinotecan against Colon Cancer Cells with or without Irinotecan Resistance

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Hyun Joo Jang ◽  
Eun Mi Hong ◽  
Juah Jang ◽  
Jung Eun Choi ◽  
Se Woo Park ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Synergistic Effects ◽  
Combined Treatment ◽  
Molar Ratio ◽  
Colon Cancer Cells ◽  
Activity Assay ◽  
Ht 29

Aims. We here investigated whether the combination of simvastatin and irinotecan could induce the synergistic effect on colon cancer cells with or without resistance to irinotecan.Methods. We investigated cell proliferation assay and assessed cell death detection ELISA and caspase-3 activity assay of various concentrations of simvastatin and irinotecan to evaluate the efficacy of drug combination on colon cancer cells with or without irinotecan resistance.Results. The IC50values of simvastatin alone and irinotecan alone were115.4±0.14 μM (r=0.98) and62.5±0.18 μM (r=0.98) in HT-29 cells without resistance to irinotecan. The IC50values of these two drugs were221.9±0.22 μM (r=0.98) and195.9±0.16 μM (r=0.99), respectively, in HT-29 cell with resistance to irinotecan. The results of combinations of the various concentrations of two drugs showed that combined treatment with irinotecan and simvastatin more efficiently suppressed cell proliferation of HT-29 cells even with resistance to irinotecan as well as without resistance. Furthermore, the combination of simvastatin and irinotecan at2:1molar ratio showed the best synergistic interaction.Conclusion. Simvastatin could act synergistically with irinotecan to overcome irinotecan resistance of colon cancer.

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

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dongxiao Jiang ◽  
Shufei Ding ◽  
Zhujun Mao ◽  
Liyan You ◽  
Yeping Ruan
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Time Dependent ◽  
Integrated Analysis ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Dapi Staining ◽  
Aloe Emodin

Abstract Background Colon 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. Methods We 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. Results The 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. Conclusion These results indicate that aloe-emodin may induce the apoptosis of human colon cancer cells through mitochondria-related pathways.

scholarly journals Antiproliferative and apoptosis-inducing effects of maslinic and oleanolic acids, two pentacyclic triterpenes from olives, on HT-29 colon cancer cells

2008 ◽  
Vol 100 (1) ◽  
pp. 36-43 ◽  
Author(s):  
M. Emília Juan ◽  
Joana M. Planas ◽  
Valentina Ruiz-Gutierrez ◽  
Hannelore Daniel ◽  
Uwe Wenzel
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Oleanolic Acid ◽  
Caspase 3 ◽  
Hydroxyl Group ◽  
Colon Cancer Cells ◽  
Maslinic Acid ◽  
Olive Fruit ◽  
Pentacyclic Triterpenes ◽  
Ht 29

We have previously reported the anticarcinogenic effects of an olive fruit extract composed of pentacyclic triterpenes, the main components of which are maslinic acid (73·25 %) and oleanolic acid (25·75 %). Here we examined the effects of the individual components on proliferation, necrosis and apoptosis rates by fluorescence-based techniques in human HT-29 colon cancer cells. Oleanolic acid showed moderate antiproliferative activity, with an ec50 of 160·6 (se 10·6) μmol/l, and moderate cytotoxicity at high concentrations ( ≥ 250 μmol/l). On the other hand, maslinic acid inhibited cell growth with an ec50 of 101·2 (se 7·8) μmol/l, without necrotic effects. Oleanolic acid, which lacks a hydroxyl group at the carbon 2 position, failed to activate caspase-3 as a prime apoptosis protease. In contrast, maslinic acid increased caspase-3-like activity at 10, 25 and 50 μmol/l by 3-, 3·5- and 5-fold over control cells, respectively. The detection of ROS in the mitochondria, which serve as pro-apoptotic signal, evidenced the different bioactivity of the two triterpenes. Confocal microscopy analysis revealed that maslinic acid generated superoxide anions while oleanolic acid-treated cells did not differ from the control. Completion of apoptosis by maslinic acid was confirmed microscopically by the increase in plasma membrane permeability, and detection of DNA fragmentation. In conclusion, the anticancer activity observed for olive fruit extracts seems to originate from maslinic acid but not from oleanolic acid. Maslinic acid therefore is a promising new compound for the chemoprevention of colon cancers.

scholarly journals AS601245, an Anti-Inflammatory JNK Inhibitor, and Clofibrate Have a Synergistic Effect in Inducing Cell Responses and in Affecting the Gene Expression Profile in CaCo-2 Colon Cancer Cells

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Angelo Cerbone ◽  
Cristina Toaldo ◽  
Stefania Pizzimenti ◽  
Piergiorgio Pettazzoni ◽  
Chiara Dianzani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Combined Treatment ◽  
Colon Cancer Cells ◽  
Positive Interaction ◽  
Anti Inflammatory

PPARαs are nuclear receptors highly expressed in colon cells. They can be activated by the fibrates (clofibrate, ciprofibrate etc.) used to treat hyperlipidemia. Since PPARαtranscriptional activity can be negatively regulated by JNK, the inhibition of JNK activity could increase the effectiveness of PPARαligands. We analysed the effects of AS601245 (a JNK inhibitor) and clofibrate alone or in association, on proliferation, apoptosis, differentiation and the gene expression profile of CaCo-2 human colon cancer cells. Proliferation was inhibited in a dose-dependent way by clofibrate and AS601245. Combined treatment synergistically reduced cell proliferation, cyclin D1 and PCNA expression and induced apoptosis and differentiation. Reduction of cell proliferation, accompanied by the modulation of p21 expression was observed in HepG2 cells, also. Gene expression analysis revealed that some genes were highly modulated by the combined treatment and 28 genes containing PPRE were up-regulated, while clofibrate alone was ineffective. Moreover, STAT3 signalling was strongly reduced by combined treatment. After combined treatment, the binding of PPARαto PPRE increased and paralleled with the expression of the PPAR coactivator MED1. Results demonstrate that combined treatment increases the effectiveness of both compounds and suggest a positive interaction between PPARαligands and anti-inflammatory agents in humans.

scholarly journals Synergistic Combinations of Curcumin, Sulforaphane, and Dihydrocaffeic Acid against Human Colon Cancer Cells

2020 ◽  
Vol 21 (9) ◽  
pp. 3108 ◽  
Author(s):  
Jesús Santana-Gálvez ◽  
Javier Villela-Castrejón ◽  
Sergio O. Serna-Saldívar ◽  
Luis Cisneros-Zevallos ◽  
Daniel A. Jacobo-Velázquez
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Synergistic Effects ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Acid Metabolite ◽  
Human Colon Cancer ◽  
Human Colon Cancer Cells ◽  
Synergistic Combinations ◽  
Ht 29

Nutraceutical combinations that act synergistically could be a powerful solution against colon cancer, which is the second deadliest malignancy worldwide. In this study, curcumin (C), sulforaphane (S), and dihydrocaffeic acid (D, a chlorogenic acid metabolite) were evaluated, individually and in different combinations, over the viability of HT-29 and Caco-2 colon cancer cells, and compared against healthy fetal human colon (FHC) cells. The cytotoxic concentrations to kill 50%, 75%, and 90% of the cells (CC50, CC75, and CC90) were obtained, using the MTS assay. Synergistic, additive, and antagonistic effects were determined by using the combination index (CI) method. The 1:1 combination of S and D exerted synergistic effects against HT-29 at 90% cytotoxicity level (doses 90:90 µM), whereas CD(1:4) was synergistic at all cytotoxicity levels (9:36–34:136 µM) and CD(9:2) at 90% (108:24 µM) against Caco-2 cells. SD(1:1) was significantly more cytotoxic for cancer cells than healthy cells, while CD(1:4) and CD(9:2) were similarly or more cytotoxic for healthy cells. Therefore, the SD(1:1) combination was chosen as the best. A model explaining SD(1:1) synergy is proposed. SD(1:1) can be used as a basis to develop advanced food products for the prevention/co-treatment of colon cancer.

scholarly journals Chrysobalanus icaco L. Anthocyanins Reduced Cell Proliferation and Inflammation in HT‐29 Colon Cancer Cells

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Vinicius Venancio ◽  
Paula Cipriano ◽  
Hyemee Kim ◽  
Adriana Mercadante ◽  
Maria de Lourdes Bianchi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Colon Cancer Cells ◽  
Ht 29

scholarly journals Tetrandrine inhibits colon carcinoma HT-29 cells growth via the Bcl-2/Caspase 3/PARP pathway and G1/S phase

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
JiaNan Li ◽  
QiuHong Wang ◽  
ZhiBin Wang ◽  
Na Cui ◽  
BingYou Yang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Molecular Docking ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Caspase 8 ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Ht 29 ◽  
Active Caspase

Abstract Tetrandrine (Tet) bisbenzylisoquinoline alkaloids isolated from Stephania tetrandra and other related species of Menispermaceae. It has been demonstrated to have positive therapeutic effects on cardiovascular disease, hypertension, silicosis, autoimmune diseases. In recent years, some reports have shown that Tet has anticancer activity in human cancers. To explore the pharmacological activity and mechanism of Tet on colon cancer and its unique advantages as a natural product. In the present study, analyses of the cell cycle, apoptosis, targets prediction, molecular docking, and alterations in protein levels were performed to elucidate how Tet functions in colon cancer. We found that Tet robustly induced arrest at the G1 phase in colon cancer cell line HT-29. It induced HT-29 cell apoptosis in a dose-dependent manner. Similarly, analysis of protein expression levels in HT-29 cells showed down-regulation of Bcl-2, pro-caspase 3, pro-caspase 8, PARP, cyclin D1 (CCND1), cyclin-dependent kinase 4 (CDK 4), and up-regulation of Bax, active caspase 3, and active caspase 8. These results indicate that Tet induces apoptosis of colon cancer cells through the mitochondrial pathway and caspase family pathway. Molecular docking showed interaction effects and binding energy. Comparing with the CDK4 inhibitors ribociclib and palbociclib, the docking energy is similar to the docked amino acid residues. Therefore, we conclude that Tet and the CCND1/CDK4 compound could form hydrogen bonds and a stable compound structure, which can inhibit colon cancer cells proliferation by regulating CCND1/CDK4 compound and its downstream proteins phosphorylated Rb (p-Rb). In summary, Tet may be a potential drug for colon cancer therapy.

scholarly journals The Mechanism of Aloe-emodin in the Treatment of Colon Cancer based on Network Pharmacological Analysis

2020 ◽  
Author(s):  
Dongxiao Jiang ◽  
Shufei Ding ◽  
Zhujun Mao ◽  
Liyan You ◽  
yeping ruan
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Time Dependent ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Dapi Staining ◽  
Wide Range ◽  
Aloe Emodin

Abstract Background: Colon cancer is a malignant gastrointestinal tumor with a high incidence, high mortality and high metastasis in the world. Aloe-emodin is a monomer compound derived from hydroxyanthraquinone. It makes a wide range of anti-tumor effects and exists in Rhubarb, Aloe, and other plants. However, the mechanism of aloe-emodin against colon cancer still not clear. Here, we predict the potential targets and mechanisms of aloe-emodin based on network pharmacology analysis. Methods: First, determine the intersection target of aloe-emodin and colon cancer, analyze and construct PPI, Gene Ontology, and KEGG pathway analysis. In addition, we selected apoptosis pathways for experimental verification including cell viability determination, cell proliferation, caspase-3 activity determination, DAPI staining, cell cycle determination and western blot to evaluate the apoptosis effect of aloe-emodin on colon cancer cells.Results: The MTT assay and cell colony experiment showed that AE inhibited cell proliferation (P<0.01). DAPI staining confirmed that AE induced apoptosis. AE activates caspase-3, caspase-9 and Bax and down-regulates the expression of Bcl-2. Furthermore, the expression level of cytochrome C protein increased in a time-dependent manner in the cytoplasm but fell in a time-dependent manner in the mitochondria.Conclusion: These results indicate that aloe-emodin may induce apoptosis of human colon cancer cells through mitochondrial related pathways.

scholarly journals KRAS-mutant colon cancer cells respond to combined treatment of ABT263 and axitinib

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Guihua Wang ◽  
Ying Huang ◽  
Zhipeng Wu ◽  
Chunmei Zhao ◽  
Hui Cong ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Small Molecules ◽  
Cancer Cells ◽  
Synergistic Effects ◽  
Combined Treatment ◽  
Colon Cancer Cells ◽  
Oncogene Addiction ◽  
In Vivo Growth

Abstract Significant challenges to develop selective and effective pharmacological inhibitors for important oncoproteins like RAS continue impeding the success to treat cancers driven by such mutations. In the present study, the ABT263 and axitinib combination imposed synergistic effects on RAS-mutant colon cancer cells. The combination inhibited in vitro and in vivo growth of the cancer cells by enhancing apoptosis. Furthermore, AKT and Wnt/β-catenin signaling pathways were slightly down-regulated by the combination in KRAS-mutant colon cancer cells. The current results indicate that oncogene addiction can be targeted for therapy in colon cancer cells harboring the RAS-mutant. Therefore, targeting oncogene addiction can be a viable strategy for treating refractory cancers driven by important oncogenes, such as KRAS, which are otherwise difficult to be targeted by small molecules.

scholarly journals Cost Effective Use of a Thiosulfinate-Enriched Allium sativum Extract in Combination with Chemotherapy in Colon Cancer

2020 ◽  
Vol 21 (8) ◽  
pp. 2766
Author(s):  
Jose Manuel Perez-Ortiz ◽  
Eva Maria Galan-Moya ◽  
Miguel Angel de la Cruz-Morcillo ◽  
Juan Francisco Rodriguez ◽  
Ignacio Gracia ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Combined Treatment ◽  
Cost Effective ◽  
Economic Feasibility ◽  
Garlic Extract ◽  
Colon Cancer Cells ◽  
Effective Use ◽  
The Impact ◽  
Ht 29

In this work, we sought to investigate the effects of a thiosulfinate-enriched garlic extract, co-administered with 5-fluorouracil (5-FU) or oxaliplatin chemotherapy, on the viability of colon cancer cells (Caco-2 and HT-29). We also addressed the economic feasibility of a new combined treatment of this thiosulfinate-enriched garlic extract, with oxaliplatin that could reduce the dosage and costs of a monotherapy. The thiosulfinate-enriched garlic extract not only enhanced the impact of 5-FU and oxaliplatin (500 µM) in decreasing Caco-2 and HT-29 viability, but also showed a higher effect than standard 5-FU and oxaliplatin chemotherapy as anti-cancer agents. These results provided evidences for the combination of lyophilized garlic extract and 5-FU or oxaliplatin as a novel chemotherapy regimen in colon cancer cells that may also reduce the clinical therapy costs.

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