scholarly journals The Combined Use of Phenothiazines and Statins Strongly Affects Doxorubicin-Resistance, Apoptosis, and Cox-2 Activity in Colon Cancer Cells

2019 ◽  
Vol 20 (4) ◽  
pp. 955 ◽  
Author(s):  
Kamila Środa-Pomianek ◽  
Krystyna Michalak ◽  
Anna Palko-Łabuz ◽  
Anna Uryga ◽  
Piotr Świątek ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Colon Cancer Cells ◽  
Phenothiazine Derivatives ◽  
Component Mixture ◽  
P Glycoprotein ◽  
Novel Approach ◽  
Combined Use ◽  
Cox 2

Since none of the multidrug resistance (MDR) modulators tested so far found their way into clinic, a novel approach to overcome the MDR of cancer cells has been proposed. The combined use of two MDR modulators of dissimilar mechanisms of action was suggested to benefit from the synergy between them. The effect of three phenothiazine derivatives that were used as single agents and in combination with simvastatin on cell growth, apoptosis induction, activity, and expression of cyclooxygenase-2 (COX-2) in doxorubicin-resistant colon cancer cells (LoVo/Dx) was investigated. Treatment of LoVo/Dx cells by phenothiazine derivatives combined with simvastatin resulted in an increase of doxorubicin cytotoxicity and its intracellular accumulation as compared to the treatment with phenothiazine derivatives that were used as single agents. Similarly, LoVo/Dx cells treated with two-component mixture of modulators showed the reduced expression of ABCB1 (P-glycoprotein) transporter and COX-2 enzyme, both on mRNA and protein level. Reduced expression of anti-apoptotic Bcl-2 protein and increased expression of pro-apoptotic Bax were also detected. Additionally, COX-2 activity was diminished, and caspase-3 activity was increased to a higher extent by phenothiazine derivative:simvastatin mixtures than by phenothiazine derivatives themselves. Therefore, the introduction of simvastatin strengthened the anti-MDR, anti-inflammatory, and pro-apoptotic properties of phenothiazines in LoVo/Dx cells.

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 THE INHIBITION OF POLYISOPRENOIDS FROM NYPA FRUTICANS LEAVES ON CYCLOOXYGENASE 2 EXPRESSION OF WIDR COLON CANCER CELLS

2018 ◽  
Vol 11 (8) ◽  
pp. 154 ◽  
Author(s):  
Dini Permata Sari ◽  
Mohammad Basyuni ◽  
Poppy Anjelisa Zaitun Hasibuan ◽  
Ridha Wati
Keyword(s):  
Colon Cancer ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Colon Cancer Cell ◽  
Cyclooxygenase 2 ◽  
Colon Cancer Cells ◽  
Chemopreventive Agents ◽  
Nypa Fruticans ◽  
Diphenyltetrazolium Bromide ◽  
Cox 2

Objective: The objective of the study was to investigate the inhibitory activity of polyisoprenoids from Nypa fruticans leaves on the expression of cyclooxygenase 2 (COX-2) against colon cancer cells.Methods: Anticancer activity performed was tested by dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method on colon cancer cell WiDr. The expression of COX-2 was observed by the immunocytochemistry method.Result: Polyisoprenoids from N. fruticans leaves exhibit anticancer activity on WiDr cells through inhibition of COX-2 expression with IC50 180.186±7.16 μg/ml.Conclusions: This study showed that polyisoprenoids from N. fruticans leaves promise chemopreventive agents for colon cancer through COX-2 inhibition.

scholarly journals Ceramide synthase 6 modulates TRAIL sensitivity and nuclear translocation of active caspase-3 in colon cancer cells

Oncogene ◽  
2009 ◽  
Vol 28 (8) ◽  
pp. 1132-1141 ◽  
Author(s):  
S White-Gilbertson ◽  
T Mullen ◽  
C Senkal ◽  
P Lu ◽  
B Ogretmen ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Nuclear Translocation ◽  
Ceramide Synthase ◽  
Colon Cancer Cells ◽  
Trail Sensitivity ◽  
Active Caspase

scholarly journals Caspase-3 regulates the migration, invasion and metastasis of colon cancer cells

2018 ◽  
Vol 143 (4) ◽  
pp. 921-930 ◽  
Author(s):  
Min Zhou ◽  
Xinjian Liu ◽  
Zonghai Li ◽  
Qian Huang ◽  
Fang Li ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Colon Cancer Cells ◽  
Invasion And Metastasis

miRNA-29a reverses P-glycoprotein-mediated drug resistance and inhibits proliferation via up-regulation of PTEN in colon cancer cells

2020 ◽  
Vol 880 ◽  
pp. 173138 ◽  
Author(s):  
Xiaoxin Shi ◽  
Amir Valizadeh ◽  
Seyed Mostafa Mir ◽  
Zatollah Asemi ◽  
Ansar Karimian ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Colon Cancer Cells ◽  
P Glycoprotein

Dual regulation of IGF-1 receptor expression by COX-2 and angiotensin II in colon cancer cells: A possible implication for cancer chemoprevention

2001 ◽  
Vol 120 (5) ◽  
pp. A594
Author(s):  
Masakazu Yasumaru ◽  
Shingo Tsuji ◽  
Masahiko Tsujii ◽  
Naoki Kawai ◽  
Arata Kimura ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Angiotensin Ii ◽  
Cancer Cells ◽  
Cancer Chemoprevention ◽  
Receptor Expression ◽  
Colon Cancer Cells ◽  
Cox 2

Effect of polyamide nanoparticles on apoptosis of colon cancer cells induced by survivin antisense oligonucleotide

2020 ◽  
Vol 10 (9) ◽  
pp. 1573-1580
Author(s):  
Yongqiang Xu ◽  
Weibiao Ye ◽  
Chan Zhou ◽  
Yuling Li ◽  
Jianfang He
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
P38 Mapk ◽  
Caspase 3 ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Significant Difference ◽  
Microfilament System ◽  
Human Colon Cancer Cells

In this study, we aimed to observe the effect of polyamidoamine (PAMAM) liposomes on the apoptosis of human colon cancer cells induced by survivin antisense oligonucleotides (ASODNs). PAMAM liposomes and PAMAM were mixed with survivin ASODNs to obtain antisense gene transfection complexes. In addition, the zeta potentials and encapsulation rates of the complexes were measured. The two gene-containing complexes were transfected into HT-29 colon cancer cells to observe changes in cell morphology, detect the inhibitory effect on tumor cells and changes in apoptosis, and observe changes in the cytoskeleton microfilament system using laser confocal microscopy. Caspase-3 activity in the cells was determined using a kinase activity assay, and p38 mitogen-activated protein kinase (p38 MAPK) activity in the cells was measured using immunoprecipitation analysis. The results showed that the zeta potential of the PAMAM liposome-survivin-ASODN complex was higher than that of the PAMAM-survivin-ASODN complex (P < 0.05). There was no significant difference in the gene encapsulation rates between the two complexes (P > 0.05). PAMAM liposomes may efficiently deliver survivin ASODNs to human colon cancer cells, reduce the expression of survivin protein and at the same time induce G2/M phase arrest in cells, and activate caspase-3 by activating p38 MAPK. Cleavage of caspase-3 destroys the structure of the intracellular skeletal microfilament system, finally resulting in apoptosis of colon cancer cells.

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