scholarly journals ROS-Dependent ER Stress and Autophagy Mediate the Anti-Tumor Effects of Tributyltin (IV) Ferulate in Colon Cancer Cells

2020 ◽  
Vol 21 (21) ◽  
pp. 8135 ◽  
Author(s):  
Adriana Celesia ◽  
Ornella Morana ◽  
Tiziana Fiore ◽  
Claudia Pellerito ◽  
Antonella D’Anneo ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Er Stress ◽  
Cancer Cells ◽  
Cancer Therapeutics ◽  
Antioxidant Response ◽  
Related Factor ◽  
Potential Candidate ◽  
Colon Cancer Cells ◽  
Rapid Generation ◽  
New Perspective

Organotin compounds represent potential cancer therapeutics due to their pro-apoptotic action. We recently synthesized the novel organotin ferulic acid derivative tributyltin (IV) ferulate (TBT-F) and demonstrated that it displays anti-tumor properties in colon cancer cells related with autophagic cell death. The purpose of the present study was to elucidate the mechanism of TBT-F action in colon cancer cells. We specifically show that TBT-F-dependent autophagy is determined by a rapid generation of reactive oxygen species (ROS) and correlated with endoplasmic reticulum (ER) stress. TBT-F evoked nuclear factor erythroid-2 related factor 2 (Nrf2)-mediated antioxidant response and Nrf2 silencing by RNA interference markedly increased the anti-tumor efficacy of the compound. Moreover, as a consequence of ROS production, TBT-F increased the levels of glucose regulated protein 78 (Grp78) and C/EBP homologous protein (CHOP), two ER stress markers. Interestingly, Grp78 silencing produced significant decreasing effects on the levels of the autophagic proteins p62 and LC3-II, while only p62 decreased in CHOP-silenced cells. Taken together, these results indicate that ROS-dependent ER stress and autophagy play a major role in the TBT-F action mechanism in colon cancer cells and open a new perspective to consider the compound as a potential candidate for colon cancer treatment.

scholarly journals The Novel Curcumin Derivative 1g Induces Mitochondrial and ER-Stress-Dependent Apoptosis in Colon Cancer Cells by Induction of ROS Production

2021 ◽  
Vol 11 ◽  
Author(s):  
Hao Wang ◽  
Yingxing Xu ◽  
Jialin Sun ◽  
Zhongguo Sui
Keyword(s):  
Colon Cancer ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Potential Candidate ◽  
The Novel ◽  
Colon Cancer Cells ◽  
Stress Dependent ◽  
Curcumin Derivative

Reactive oxygen species (ROS) play an important role in cellular metabolism. Many chemotherapeutic drugs are known to promote apoptosis through the production of ROS. In the present study, the novel curcumin derivative, 1g, was found to inhibit tumor growth in colon cancer cells both in vitro and in vivo. Bioinformatics was used to analyze the differentially expressed mRNAs. The mechanism of this effect was a change in mitochondrial membrane potential caused by 1g that increased its pro-apoptotic activity. In addition, 1g produced ROS, induced G1 checkpoint blockade, and enhanced endoplasmic reticulum (ER)-stress in colon cancer cells. Conversely, pretreatment with the ROS scavenging agent N-acetyl-l-cysteine (NAC) inhibited the mitochondrial dysfunction caused by 1g and reversed ER-stress, cell cycle stagnation, and apoptosis. Additionally, pretreatment with the p-PERK inhibitor GSK2606414 significantly reduced ER-stress and reversed the apoptosis induced by colon cancer cells. In summary, the production of ROS plays an important role in the destruction of colon cancer cells by 1g and demonstrates that targeted strategies based on ROS represent a promising approach to inhibit colon cancer proliferation. These findings reveal that the novel curcumin derivative 1g represents a potential candidate therapeutics for the treatment of colon cancer cells, via apoptosis caused by mitochondrial dysfunction and endoplasmic reticulum stress.

scholarly journals Marine Peroxy Sesquiterpenoids Induce Apoptosis by Modulation of Nrf2-ARE Signaling in HCT116 Colon Cancer Cells

Marine Drugs ◽  
2018 ◽  
Vol 16 (10) ◽  
pp. 347 ◽  
Author(s):  
Junsei Taira ◽  
Haruna Miyazato ◽  
Katsuhiro Ueda
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
B Cell Lymphoma ◽  
Human Colon ◽  
Antioxidant Response ◽  
Heme Oxygenase 1 ◽  
H2o2 Production ◽  
Related Factor ◽  
Colon Cancer Cells ◽  
Human Colon Cancer

Our current study demonstrated that the marine peroxy sesquiterpenoids isolated from the Okinawan soft coral Sinularia sp. have an antitumor activity in human colon cancer cell (HCT) 116 colon cancer cells with their induction of apoptosis due to H2O2 production derived from the compounds. This study clarified that peroxy sesquiterpenoids (1 and 2) inhibited anti-apoptosis proteins, such as B-cell lymphoma-extra large (Bcl-xL) and phosphoAkt (pAkt). In addition, the heme oxygenase-1 (HO-1), nuclear factor-erythroid-2-related factor (Nrf2), and phosphoNrf2 (pNrf2) proteins related to the cell survival regulation signal of Nrf2-ARE (antioxidant response element) were also suppressed in the presence of these compounds. While the cells treated with the compounds and trolox as an antioxidant expressed the inhibited proteins, such as HO-1, Nrf2, and Bcl-xL, it was suggested that the H2O2 involving free radical reactions derived from the molecule would be a trigger of apoptosis with the modulation of Nrf2-ARE signaling in the cells.

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.

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 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

scholarly journals Correction: Co-targeting translation and proteasome rapidly kills colon cancer cells with mutant RAS/RAF via ER stress

Oncotarget ◽  
2018 ◽  
Vol 9 (6) ◽  
pp. 7271-7271
Author(s):  
Xiangyun Li ◽  
Mei Li ◽  
Hang Ruan ◽  
Wei Qiu ◽  
Xiang Xu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Er Stress ◽  
Cancer Cells ◽  
Colon Cancer Cells
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