Epibrassinolide Treatment Caused Autophagy or Apoptosis Decision in a Time-Dependent Manner through ER Stress in Colon Cancer Cells

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

10.21203/rs.3.rs-136416/v1 ◽

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.

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FTIR microspectroscopic analysis of sodium butyrate induced differentiation in colon cancer cells in a time‐dependent manner

The FASEB Journal ◽

10.1096/fasebj.27.1_supplement.1006.4 ◽

2013 ◽

Vol 27 (S1) ◽

Author(s):

Nihal Simsek Ozek ◽

Seher Gok ◽

Sreeparna Banerjee ◽

Feride Severcan

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Sodium Butyrate ◽

Time Dependent ◽

Dependent Manner ◽

Colon Cancer Cells ◽

Induced Differentiation

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Growth Inhibition by Caffeic Acid, One of the Phenolic Constituents of Honey, in HCT 15 Colon Cancer Cells

The Scientific World JOURNAL ◽

10.1100/2012/372345 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 25

Author(s):

Saravana Kumar Jaganathan

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Caffeic Acid ◽

Mtt Assay ◽

Time Dependent ◽

Ros Generation ◽

Dependent Manner ◽

Colon Cancer Cells ◽

Phenolic Constituents ◽

Induced Apoptosis

Previous work from our laboratory showed that the mechanism of crude-honey induced apoptosis in colon cancer cells. Since phenolic constituents of honey were attributed to its apoptosis-inducing ability, we studied caffeic acid, one of the phenolic constituents of honey, induced effect on colon cancer cells. Antiproliferative effect of caffeic acid was estimated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. MTT assay signified the antiproliferative nature of caffeic acid against the HCT 15 colon cancer cells. A time-dependent inhibition of colony formation was evident with caffeic acid treatment. Cell-cycle analysis of caffeic acid- (CA-) treated cells indicated increasing accumulation of cells at sub-G1phase. Photomicrograph images of treated cells showed membrane blebbing and cell shrinkage. Yo-pro-1 staining of caffeic-acid-treated cells confirmed apoptosis in dose- and time-dependent manner. Increasing ROS generation and reduction in the mitochondrial membrane potential were also accompanied in the caffeic acid-induced apoptosis. This work will promote caffeic acid as a likely candidate in the chemoprevention of colon cancer.

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Autophagy Induction by Trichodermic Acid Attenuates Endoplasmic Reticulum Stress-Mediated Apoptosis in Colon Cancer Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22115566 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5566

Author(s):

Junyan Qu ◽

Cheng Zeng ◽

Tingting Zou ◽

Xu Chen ◽

Xiaolong Yang ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Er Stress ◽

Cancer Cells ◽

Protective Mechanism ◽

Dependent Manner ◽

Colon Cancer Cells ◽

Antitumor Effects

Colorectal cancer (CRC) is the third leading malignant tumor in the world, which has high morbidity and mortality. In this study we found that trichodermic acid (TDA), a secondary metabolite isolated from the plant endophytic fungus Penicillium ochrochloronthe with a variety of biological and pharmacological activities, exhibited the antitumor effects on colorectal cancer cells in vitro and in vivo. Our results showed that TDA inhibited the proliferation of colon cancer cells in a dose-dependent manner. TDA induces sustained endoplasmic reticulum stress, which triggers apoptosis through IRE1α/XBP1 and PERK/ATF4/CHOP pathways. In addition, we found that TDA mediated endoplasmic reticulum stress also induces autophagy as a protective mechanism. Moreover, combined treatment of TDA with autophagy inhibitors significantly enhanced its anticancer effect. In conclusion, our results indicated that TDA can induce ER stress and autophagy mediated apoptosis, suggesting that targeting ER stress and autophagy may be an effective strategy for the treatment of CRC.

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Lack of functional p53 renders DENSpm-induced autophagy and apoptosis in time dependent manner in colon cancer cells

Amino Acids ◽

10.1007/s00726-014-1851-7 ◽

2014 ◽

Vol 47 (1) ◽

pp. 87-100 ◽

Cited By ~ 3

Author(s):

Ajda Çoker-Gürkan ◽

Elif Damla Arisan ◽

Pınar Obakan ◽

Narçin Palavan-Unsal

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Time Dependent ◽

Dependent Manner ◽

Colon Cancer Cells

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Purvalanol induces endoplasmic reticulum stress-mediated apoptosis and autophagy in a time-dependent manner in HCT116 colon cancer cells

Oncology Reports ◽

10.3892/or.2015.3918 ◽

2015 ◽

Vol 33 (6) ◽

pp. 2761-2770 ◽

Cited By ~ 6

Author(s):

AJDA COKER-GÜRKAN ◽

ELIF DAMLA ARISAN ◽

PINAR OBAKAN ◽

KÜBRA AKALIN ◽

UTKU ÖZBEY ◽

...

Keyword(s):

Colon Cancer ◽

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Cancer Cells ◽

Time Dependent ◽

Dependent Manner ◽

Colon Cancer Cells

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Faculty Opinions recommendation of DHA induces ER stress and growth arrest in human colon cancer cells: associations with cholesterol and calcium homeostasis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1115344.571363 ◽

2008 ◽

Author(s):

Kishor M Wasan

Keyword(s):

Colon Cancer ◽

Er Stress ◽

Cancer Cells ◽

Calcium Homeostasis ◽

Growth Arrest ◽

Human Colon ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Human Colon Cancer Cells

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Colorectal Cancer Apoptosis Induced by Dietary δ-Valerobetaine Involves PINK1/Parkin Dependent-Mitophagy and SIRT3

International Journal of Molecular Sciences ◽

10.3390/ijms22158117 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8117

Author(s):

Nunzia D’Onofrio ◽

Elisa Martino ◽

Luigi Mele ◽

Antonino Colloca ◽

Martina Maione ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Mitochondrial Dysfunction ◽

Cancer Cells ◽

Current Knowledge ◽

Apoptotic Cell ◽

Critical Role ◽

Dependent Manner ◽

Colon Cancer Cells ◽

Protein Levels

Understanding the mechanisms of colorectal cancer progression is crucial in the setting of strategies for its prevention. δ-Valerobetaine (δVB) is an emerging dietary metabolite showing cytotoxic activity in colon cancer cells via autophagy and apoptosis. Here, we aimed to deepen current knowledge on the mechanism of δVB-induced colon cancer cell death by investigating the apoptotic cascade in colorectal adenocarcinoma SW480 and SW620 cells and evaluating the molecular players of mitochondrial dysfunction. Results indicated that δVB reduced cell viability in a time-dependent manner, reaching IC50 after 72 h of incubation with δVB 1.5 mM, and caused a G2/M cell cycle arrest with upregulation of cyclin A and cyclin B protein levels. The increased apoptotic cell rate occurred via caspase-3 activation with a concomitant loss in mitochondrial membrane potential and SIRT3 downregulation. Functional studies indicated that δVB activated mitochondrial apoptosis through PINK1/Parkin pathways, as upregulation of PINK1, Parkin, and LC3B protein levels was observed (p < 0.0001). Together, these findings support a critical role of PINK1/Parkin-mediated mitophagy in mitochondrial dysfunction and apoptosis induced by δVB in SW480 and SW620 colon cancer cells.

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γ-Synuclein is Closely Involved in Autophagy that Protects Colon Cancer Cell from Endoplasmic Reticulum Stress

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666210119093327 ◽

2021 ◽

Vol 21 ◽

Author(s):

Qing Ye ◽

Yuanfei Peng ◽

Feng Huang ◽

Jinhu Chen ◽

Yangmei Xu ◽

...

Keyword(s):

Colon Cancer ◽

Western Blot ◽

Er Stress ◽

Cancer Cells ◽

Early Stage ◽

Colon Cancer Cell ◽

Colon Cancer Cells ◽

Rt Pcr ◽

Jnk Pathway ◽

Hct116 Cells

Background: In previous studies, we provided evidence suggesting the involvement of γ-synuclein in growth, invasion, and metastasis of colon cancer cells in vitro and in vivo. Among γ-synuclein downstream genes, the microtubule-associated protein 1 light chain 3 (LC3), an autophagy gene, was screened by gene expression profile chip analysis. Objective: We planned to investigate the functional effects of γ-synuclein on autophagy induced by ER stress in colon cancer cells. Methods: We investigated the functional effects of γ-synuclein on autophagy and apoptosis induced by Thapsigargin (TG), ER stressinducing agent, in colon cancer cell lines using immunofluorescence staining, RT-PCR, western blot, CCK8 test, flow cytometry analysis, and transmission electron microscopy. To further determine how γ-synuclein regulated autophagy and apoptosis, PD98059 (ERK inhibitor), SP600125 (ERK inhibitor), anisomycin (JNK activator), and c-Jun siRNA were used respectively in γ-synuclein siRNA transfected HCT116 cells. Then, autophagy proteins, apoptosis proteins, and pathway proteins were detected by western blot analysis. The expression of autophagy genes was assessed by RT-PCR. Results: Our data showed that ER stress-induced colon cancer cells autophagy mainly in the early stage (0-24h) and apoptosis mainly in the late stage (24-48h). ER stress up-regulated γ-synuclein gene and protein expression in colon cancer cells, accompanied by autophagy. γ-synuclein protected HCT116 cells by enhancing autophagy in the early stage (0-24h) through activation of ERK and JNK pathway and inhibiting apoptosis in the late stage (24-48h) through inhibition of the JNK pathway. γ-synuclein could promote autophagy via the JNK pathway activation of ATG genes, LC3, Beclin 1, and ATG7. γ-synuclein may play a role in the transition between autophagy and apoptosis in our model. Conclusion: Overall, we provided the first experimental evidence to show that γ-synuclein may play an important role in autophagy that protects colon cancer cells from ER stress. Therefore, our data suggest a new molecular mechanism for γ-synuclein-mediated CRC progression.

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