PMA induces apoptosis in the SNU-C4 colon cancer cells through caspase-9 independently of caspase-3 and -8

Abstract Background: Colon cancer is a common gastrointestinal tumor with a poor prognosis, which makes it urgent to explore new therapeutic strategies. The anti-tumor effect of Plasmodium infection has been reported in some murine models, but it is not clear whether it has an anti-colon cancer effect. In this study, we investigated the anti-colon cancer effect of Plasmodium infection and its related mechanisms using a mouse model of colon cancer.Methods: An experimental model was established by intraperitoneal injection of Plasmodium yoelii-infected erythrocytes into mice with colon cancer. The size of tumors was observed dynamically in mice, and the expression of Ki67 detected by immunohistochemistry was to analyze tumor cells proliferation. Apoptosis was assessed by Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) staining, and the expression of apoptosis concerned proteins, including Bax, Bcl-2, Caspase-9, Cleaved Caspase-3, were detected by western blot and immunohistochemistry, respectively. Transmission electron microscopy (TEM) was used to observe the ultrastructural change of colon cancer cells. And the expression of mitochondrial biogenesis correlative central protein, PGC-1α, and mitophagy relevant crucial proteins, PINK1/Parkin, were detected by western blot. Results: We found that Plasmodium infection reduced the weights and sizes of tumors and decreased the expression of Ki67 in colon cancer-bearing mice. Furthermore, Plasmodium infection promoted mitochondria-mediated apoptosis in colon cancer cells, as evidenced by the increased proportion of TUNEL-positive cells, the up-regulated expression of Bax, Caspase-9, and Cleaved Caspase-3 proteins, and the down-regulated expression of Bcl-2 protein. In colon cancer cells, we found destroyed nucleus, swollen mitochondria, missing cristae, and the decreased number of autolysosomes. In addition, Plasmodium infection disturbed mitochondrial biogenesis and mitophagy through the reduced expression of PGC-1α, PINK1, and Parkin proteins in colon cancer tissues.Conclusions: Plasmodium infection can play an anti-colon cancer role in mice by inhibiting proliferation and promoting mitochondria-mediated apoptosis in colon cancer cells, which may relate to mitochondrial biogenesis and mitophagy.

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

Cancer Cell International ◽

10.1186/s12935-021-01942-8 ◽

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.

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

British Journal Of Nutrition ◽

10.1017/s0007114508882979 ◽

2008 ◽

Vol 100 (1) ◽

pp. 36-43 ◽

Cited By ~ 98

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.

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

Oncogene ◽

10.1038/onc.2008.468 ◽

2009 ◽

Vol 28 (8) ◽

pp. 1132-1141 ◽

Cited By ~ 95

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

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

International Journal of Cancer ◽

10.1002/ijc.31374 ◽

2018 ◽

Vol 143 (4) ◽

pp. 921-930 ◽

Cited By ~ 39

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

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

Materials Express ◽

10.1166/mex.2020.1769 ◽

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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Cleavage of GSDME by caspase-3 determines lobaplatin-induced pyroptosis in colon cancer cells

Cell Death and Disease ◽

10.1038/s41419-019-1441-4 ◽

2019 ◽

Vol 10 (3) ◽

Cited By ~ 37

Author(s):

Junhui Yu ◽

Shan Li ◽

Jie Qi ◽

Zilu Chen ◽

Yunhua Wu ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Caspase 3 ◽

Colon Cancer Cells

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HSP90 Inhibitors, Geldanamycin and Radicicol, Enhance Fisetin-Induced Cytotoxicity via Induction of Apoptosis in Human Colonic Cancer Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/987612 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 8

Author(s):

Ming-Shun Wu ◽

Gi-Shih Lien ◽

Shing-Chuan Shen ◽

Liang-Yo Yang ◽

Yen-Chou Chen

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Caspase 3 ◽

P53 Protein ◽

Colon Cancer Cells ◽

Hsp90 Inhibitors ◽

Dna Ladder ◽

Human Colon Cancer ◽

Bax Protein

We revealed the cytotoxic effect of the flavonoid, fisetin (FIS), on human COLO205 colon cancer cells in the presence and absence of the HSP90 inhibitors, geldanamycin (GA) and radicicol (RAD). Compared to FIS treatment alone of COLO205 cells, GA and RAD significantly enhanced FIS-induced cytotoxicity, increased expression of cleaved caspase-3 and the PAPR protein, and produced a greater density of DNA ladder formation. GA and RAD also reduced the MMPs with induction of caspase-9 protein cleavage in FIS-treated COLO205 cells. Increased caspase-3 and -9 activities were detected in COLO205 cells treated with FIS+GA or FIS+RAD, and the intensity of DNA ladder formation induced by FIS+GA was reduced by adding the caspase-3 inhibitor, DEVD-FMK. A decrease in Bcl-2 but not Bcl-XL or Bax protein by FIS+GA or FIS+RAD was identified in COLO205 cells by Western blotting. A reduction in p53 protein with increased ubiquitin-tagged proteins was observed in COLO205 cells treated with FIS+GA or FIS+RAD. Furthermore, GA and RAD reduced the stability of the p53 protein in COLO205 cells under FIS stimulation. The evidence supports HSP90 inhibitors possibly sensitizing human colon cancer cells to FIS-induced apoptosis, and treating colon cancer by combining HSP90 inhibitors with FIS deserves further in vivo study.

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