scholarly journals Levistolide A Induces Apoptosis via ROS-Mediated ER Stress Pathway in Colon Cancer Cells

2017 ◽  
Vol 42 (3) ◽  
pp. 929-938 ◽  
Author(s):  
Yingjuan Yang ◽  
Yanhua Zhang ◽  
Lan Wang ◽  
Shaochin Lee
Keyword(s):  
Colon Cancer ◽  
Er Stress ◽  
Cancer Cells ◽  
Natural Compound ◽  
Chinese Herb ◽  
Colon Cancer Cells ◽  
Traditional Chinese Herb ◽  
Underlying Mechanisms ◽  
Stress Pathway ◽  
Hct116 Cells

Background/Aims: Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Levistolide A (LA), a natural compound isolated from the traditional Chinese herb Ligusticum chuanxiong Hort, is used for treating cancer. In this study, we investigated the anticancer effect of LA in HCT116 and its isogenic p53-/- colon cancer cells, as well as the underlying mechanisms. Methods: MTT assay was used to evaluate the effect of LA on the viability of cancer cells. Apoptosis and reactive oxygen species (ROS) production by the cells were determined by flow cytometry. Protein expression was detected by western blotting. Results: The results showed that LA inhibited viability and caused apoptosis of both wild-type and p53-/- HCT116 cells. LA was able to trigger production of ROS and endoplasmic reticulum (ER) stress. Inhibition of ROS using N-acetylcysteine abrogated LA-induced ER stress and apoptosis, as well as the reduction in cancer cell viability. Conclusion: Our results indicate that LA causes apoptosis of colon cancer cells via ROS-mediated ER stress pathway. It will be interesting to develop the natural compound for chemotherapy of cancers such as CRC.

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

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.

Cytotoxic Effect of the Combination of Gemcitabine and Atorvastatin Loaded in Microemulsion on the HCT116 Colon Cancer Cells

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Mayson H. Alkhatib ◽  
Dalal Al-Saedi ◽  
Wadiah S. Backer
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Therapeutic Potential ◽  
Morphological Changes ◽  
In Vitro Study ◽  
Colon Cancer Cells ◽  
Apoptosis Detection ◽  
Hct116 Cells

The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize efficacies by eradicating resistant, reduce the dosage of the drug and minimize toxicities on the normal cells. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations. The objective of this in vitro study was to evaluate the antitumor activity of the combination therapy of GEM and ATVencapsulated in a microemulsion (ME) formulation in the HCT116 colon cancer cells. The cytotoxicity and efficacy of the formulation were assessed by the 3- (4,5dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay. The mechanism of cell death was examined by observing the morphological changes of treated cells under light microscope, identifying apoptosis by using the ApopNexin apoptosis detection kit, and viewing the morphological changes in the chromatin structure stained with 4′,6-diamidino-2-phenylindole (DAPI) under the inverted fluorescence microscope. It has been found that reducing the concentration of GEM loaded on ME (GEM-ME) from 5μM to 1.67μM by combining it with 3.33μM of ATV in a ME formulation (GEM/2ATV-ME) has preserved the strong cytotoxicity of GEM-ME against HCT116 cells. The current study proved that formulating GEM with ATV in ME has improved the therapeutic potential of GEM and ATV as anticancer drugs.

scholarly journals Arachidonic acid induces ER stress and apoptosis in HT-29 human colon cancer cells

2020 ◽  
Vol 24 (5) ◽  
pp. 260-266
Author(s):  
Sijeong Bae ◽  
Min-Kyoung Kim ◽  
Hong Seok Kim ◽  
Young-Ah Moon
Keyword(s):  
Colon Cancer ◽  
Arachidonic Acid ◽  
Er Stress ◽  
Cancer Cells ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Human Colon Cancer Cells ◽  
Ht 29

scholarly journals Differential Mechanism of ATP Production Occurs in Response to Succinylacetone in Colon Cancer Cells

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3575 ◽  
Author(s):  
Lee ◽  
Woo ◽  
Yoo ◽  
Cho ◽  
Kim
Keyword(s):  
Reactive Oxygen Species ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Pyruvate Dehydrogenase ◽  
Oxygen Species ◽  
Colon Cancer Cells ◽  
Atp Production ◽  
Ht29 Cells ◽  
Differential Mechanism ◽  
Hct116 Cells

Our aim was to verify the potential ability of succinylacetone (SA) to inhibit mitochondrial function, thereby suppressing cancer cell proliferation. SA treatment caused apoptosis in HCT116 and HT29 cells, but not in SW480 cells, with mitochondria playing a key role. We checked for dysfunctional mitochondria after SA treatment. Mitochondria of HT29 cells were swollen, indicating damage, whereas in HCT116 cells, several mitochondria had a diminished size. Damaged mitochondria decreased ATP production and induced reactive oxygen species (ROS) in the cells. To understand SA-induced reduction in ATP production, we investigated the electron transfer chains (ETC) and pyruvate dehydrogenase kinase (PDK) activity, which prevents the transfer of acetyl-CoA to the TCA (tricarboxylic acid) cycle by inhibiting PDH (pyruvate dehydrogenase) activity. In each cell line, the inhibitory mechanism of ATP by SA was different. The activity of complex III consisting of the mitochondrial ETCs in HT29 cells was decreased. In contrast, PDH activity in HCT116 cells was reduced. Nicotinamide nucleotide transhydrogenase (NNT)-removing reactive oxygen species (ROS) was upregulated in HT29 cells, but not in HCT116 cells, indicating that in HT29 cells, a defense mechanism was activated against ROS. Collectively, our study showed a differential mechanism occurs in response to SA in colon cancer cells.

scholarly journals Inhibition of HSP90 by AUY922 Preferentially Kills Mutant KRAS Colon Cancer Cells by Activating Bim through ER Stress

2016 ◽  
Vol 15 (3) ◽  
pp. 448-459 ◽  
Author(s):  
Chun Yan Wang ◽  
Su Tang Guo ◽  
Jia Yu Wang ◽  
Fen Liu ◽  
Yuan Yuan Zhang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Er Stress ◽  
Cancer Cells ◽  
Colon Cancer Cells
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