Cholesterol Depletion by TASIN-1 Induces Apoptotic Cell Death through the ER Stress/ROS/JNK Signaling in Colon Cancer Cells

Zhang, Lu; Kim, Sang Bum; Luitel, Krishna; Shay, Jerry W.

doi:10.1158/1535-7163.mct-17-0887

Cited by 26 publications

(22 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Endoplasmic reticulum (ER) stress is emerging as a modulator of different pathologies and as an important mechanism contributing to cancer cell death in response to therapeutic agents [15, 16]. In several instances, oxidative stress and the onset of ER stress occur together [17, 18]. Therefore, we examined the expression of ER stress-related proteins, such as p-eIF2α and ATF4 in IATL-treated prostate cancer cells.…”

Section: Resultsmentioning

confidence: 99%

Isoalantolactone induces apoptosis through ROS-mediated ER stress and inhibition of STAT3 in prostate cancer cells

Chen

Liu

et al. 2018

J Exp Clin Cancer Res

View full text Add to dashboard Cite

BackgroundProstate cancer is one of the most commonly diagnosed cancers in men worldwide. Currently available therapies for metastatic prostate cancer are only marginally effective. Therefore, new therapeutic agents are urgently needed to improve patient outcome. Isoalantolactone (IATL), an active sesquiterpene naturally present in many vegetables and medicinal plants, is known to induce cell death and apoptosis in various cancer cell lines. Nevertheless, antitumor mechanisms initiated by IATL in cancer cells have not been fully defined.MethodsCell apoptosis and cellular ROS levels were analyzed by flow cytometry. Western blot and qRT-PCR were used to analyze the protein and mRNA levels of indicated molecules, respectively. Nude mice xenograft model was used to test the effects of IATL on prostate cancer cell growth in vivo.ResultsIn this study, we found that IATL dose-dependently inhibited cancer cell growth and induced apoptosis in PC-3 and DU145 cells. Mechanistically, our data found that IATL induced reactive oxygen species (ROS) production, resulting in the activation of endoplasmic reticulum stress pathway and eventually cell apoptosis in prostate cancer cells. IATL also decreased the protein expression levels of p-STAT3 and STAT3, and the effects of IATL were reversed by pretreatment with N-acetyl-L-cysteine (NAC). In vivo, we found that IATL inhibited the growth of prostate cancer xenografts without exhibiting toxicity. Treatment of mice bearing human prostate cancer xenografts with IATL was also associated with induction of ER stress and inhibtion of STAT3.ConclusionIn summary, our results unveil a previously unrecognized mechanism underlying the biological activity of IATL, and provide a novel anti-cancer candidate for the treatment of prostate cancer.

show abstract

Section: Resultsmentioning

confidence: 99%

Isoalantolactone induces apoptosis through ROS-mediated ER stress and inhibition of STAT3 in prostate cancer cells

Chen

Liu

et al. 2018

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…Cellular cholesterol demands are increased in tumorigenesis to support membrane synthesis, cell proliferation, and survival (Bovenga et al, 2015). Conversely, lipid depletion is associated with reduced cell viability, metastasis, and tumor burden in cell and animal models (Sharma et al, 2019; Su et al, 2012; Zhang et al, 2018), whereas lipid‐lowering therapies have shown promise in decreasing risk and improving prognosis of numerous cancer types in human populations (Bovenga et al, 2015; Couttenier et al, 2017; Mondul et al, 2018). Thus, it is essential to elucidate the complex mechanisms underlying the relationship between cancer and cellular cholesterol metabolism in order to optimize prognostic and therapeutic practices (Chimento et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Low‐Density Lipoproteins, High‐Density Lipoproteins (HDL), and HDL‐Associated Proteins Differentially Modulate Chronic Myelogenous Leukemia Cell Viability

Andersen

Dupree

Murray

et al. 2020

Lipids

View full text Add to dashboard Cite

Cellular lipid metabolism, lipoprotein interactions, and liver X receptor (LXR) activation have been implicated in the pathophysiology and treatment of cancer, although findings vary across cancer models and by lipoprotein profiles. In this study, we investigated the effects of human-derived low-density lipoproteins (LDL), highdensity lipoproteins (HDL), and HDL-associated proteins apolipoprotein A1 (apoA1) and serum amyloid A (SAA) on markers of viability, cholesterol flux, and differentiation in K562 cells-a bone marrow-derived, stem-like erythroleukemia cell model of chronic myelogenous leukemia (CML). We further evaluated whether lipoprotein-mediated effects were altered by concomitant LXR activation. We observed that LDL promoted higher K562 cell viability in a dose-and time-dependent manner and increased cellular cholesterol concentrations, while LXR activation by the agonist TO901317 ablated these effects. LXR activation in the presence of HDL, apoA1 and SAA-rich HDL suppressed K562 cell viability, while robustly inducing mRNA expression of ATP-binding cassette transporter A1 (ABCA1). HDL and its associated proteins additionally suppressed mRNA expression of anti-apoptotic B-cell lymphoma-extra large (BCL-xL), and the erythroid lineage marker 5 0-aminolevulinate synthase 2 (ALAS2), while SAA-rich HDL induced mRNA expression of the megakaryocytic lineage marker integrin subunit alpha 2b (ITGA2B). Together, these findings suggest that lipoproteins and LXR may impact the viability and characteristics of CML cells.

show abstract

“…The IHC results indicated that JNK was transcribed and expressed after 540 mg/kg ZnO NPs exposure. These two genes had been reported to induce apoptosis [29]. Meanwhile, the genes which exhibited an increase could be indicative of the ZnO NPs induction of placenta ER stress.…”

Section: Discussionmentioning

confidence: 93%

Nano Zinc Oxide Induced Fetal Mice Growth Restriction, Based on Oxide Stress and Endoplasmic Reticulum Stress

et al. 2020

View full text Add to dashboard Cite

ZnO NPs have been assessed to show adverse effects on reproductive organs, but the molecular mechanisms of reproductive toxicity have not been sufficiently studied. In this research, the dosage effects from the oral exposure of ZnO NPs (30 nm) to pregnant mice in gestation day 10.5 to 17.5 was analyzed. Pregnant mice exposed to ZnO NPs induced dam injury, mice fetal growth restriction, and the fetus number decreased. The pathological evaluation showed that ZnO NPs exposure caused placental spongiotrophoblast area decease and structural damage. The RT-qPCR and immunocytochemistry data indicated that ZnO NPs could induce placenta oxide stress, endoplasmic reticulum stress responses, apoptosis, and altered placental function. These findings indicated that ZnO NPs could induce dam injury and fetal growth restriction. Reproductive toxicity of ZnO NPs may be due to placental injury and function alteration caused by apoptosis, oxide stress, and endoplasmic reticulum stress after ZnO NPs exposure.

show abstract

Cholesterol Depletion by TASIN-1 Induces Apoptotic Cell Death through the ER Stress/ROS/JNK Signaling in Colon Cancer Cells

Cited by 26 publications

References 41 publications

Isoalantolactone induces apoptosis through ROS-mediated ER stress and inhibition of STAT3 in prostate cancer cells

Isoalantolactone induces apoptosis through ROS-mediated ER stress and inhibition of STAT3 in prostate cancer cells

Low‐Density Lipoproteins, High‐Density Lipoproteins (HDL), and HDL‐Associated Proteins Differentially Modulate Chronic Myelogenous Leukemia Cell Viability

Nano Zinc Oxide Induced Fetal Mice Growth Restriction, Based on Oxide Stress and Endoplasmic Reticulum Stress

Contact Info

Product

Resources

About