Dissociation of NSC606985 induces atypical ER-stress and cell death in prostate cancer cells

Wang, Liping; Fu, Pengcheng; Zhao, Yuan; Guo, Wei; Yu, Richard; Wang, Xin; Tang, Zehai; Imperato‐McGinley, Julianne

doi:10.3892/ijo.2016.3555

Cited by 6 publications

(2 citation statements)

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“…At the early stage of ER stress, protein synthesis within ER will be reduced, and related genes regulating protein translation and correct folding will be activated, which contributes to maintaining the normal physiological functions of cells, thus, promoting cell survival (25). However, a large amount of misfolded or unfolded proteins will be accumulated in ER in the case of excessive ER duration or UPR function impairment, at this moment, pro-apoptosis signal will be activated (26).…”

Section: Discussionmentioning

confidence: 99%

Anacardic acid induces cell apoptosis of prostatic cancer through autophagy by ER stress/DAPK3/Akt signaling pathway

et al. 2017

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Anacardic acid, which is commonly seen in plants of Anacardiaceae, is an important composition of cashew, ginkgo leaf and fruit, and it has been suggested in previous research to show antitumor activity. The main aim of the present study was to evaluate the anticancer effects of anacardic acid on cell apoptosis of prostatic cancer and molecular mechanisms of this phenomenon. In this study we found that anacardic acid inhibited cell proliferation, induced apoptosis and caspase-3/9 activities and Bax protein expression of prostatic cancer. Anacardic acid induced the ER stress inducing factors (BiP, CHOP, p-eIF2α), autophagy, LC3, Beclin-1, Atg 7 and DAPK3 protein expression, and suppressed p-Akt and p-mTOR protein expression of prostatic cancer. Si-CHOP was used to inhibit ER stress in prostatic cancer by anacardic acid, which showed that the cell proliferation was increased, apoptosis, and caspase-3/9 activities and Bax protein expression was suppressed, autophagy, LC3, Beclin-1, Atg 7 and DAPK3 protein expression was reduced, and p-Akt and p-mTOR protein expression was promoted. DAPK3 inhibited p-Akt and p-mTOR protein expression, enhanced the anticancer effects of anacardic acid on prostatic cancer through autophagy. For the first time, the present study showed that anacardic acid induces cell apoptosis of prostatic cancer through autophagy by ER stress/DAPK3/Akt signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Anacardic acid induces cell apoptosis of prostatic cancer through autophagy by ER stress/DAPK3/Akt signaling pathway

et al. 2017

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“…To determine the apoptotic pathway(s) involved in statin-induced cell apoptosis, we have analyzed representative biomarkers of intrinsic, extrinsic and ER-related apoptotic pathways, BAX and BCL-2,26,27 caspase-8 and FAS-L,28 and CHOP,29 respectively. Statins significantly increased FAS-L expression level and the cleavage of caspase-8, caspase-3 and PARP without an alteration in BAX, BCL-2 and CHOP (Figure 4), suggesting that the extrinsic death receptor pathway is the major signal pathway involved in statin-induced cell apoptosis in PCa cells, which is in agreement with the previous demonstration 30…”

Section: Discussionmentioning

confidence: 99%

<p>Statins induce cell apoptosis through a modulation of AKT/FOXO1 pathway in prostate cancer cells</p>

Deng

Zhang

Zeng

et al. 2019

CMAR

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BackgroundIn recent years, statins have been frequently investigated in neoplasms. However, the potential roles of statins on prostate cancer cells and the underlying mechanisms have not been fully elucidated. In current study, we explored the effect and molecular mechanism of statins on cell proliferation and apoptosis in prostate cancer cells.MethodsProstate cancer cell were treated with gradient doses of simvastatin and fluvastatin for 24–72 h. Cell proliferation was analyzed by using MTS assay and colony formation. Cell apoptosis was measured by Hoechst staining, ﬂow cytometry and caspase-3 activity. Western blotting was used to evaluate the proteins levels.ResultsBoth simvastatin and fluvastatin produced a dose- and time-dependent inhibition of cell viability and colony formation while a promotion of cell apoptosis as evident with increases in caspase-3 activity, cleaved-caspase-3, cleaved-caspase-8 and cleaved-PARP levels in PC3 cells. Similar statin effects were observed in DU145 prostate cancer cells. Furthermore, statins produced a time- and dose-dependent reduction of phosphorylated-AKT and phosphorylated-FOXO1 levels in PC3 cells, and pretreatment of cells with an AKT phosphorylation inhibitor, MK2206, potentiated statins’ effect.ConclusionStatins decrease cell proliferation and induce cell apoptosis, probably mediated via a downregulation of AKT/FOXO1 phosphorylation in prostate cancer cells, which may have a potential benefit in prostate cancer prevention and therapy.

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Exploring the dual role of endoplasmic reticulum stress in urological cancers: Implications for tumor progression and cell death interactions

Farahani,

Alimohammadi,

Raei

et al. 2024

Journal of Cell Communication and Signaling

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The endoplasmic reticulum (ER) is crucial for maintaining calcium balance, lipid biosynthesis, and protein folding. Disruptions in ER homeostasis, often due to the accumulation of misfolded or unfolded proteins, lead to ER stress, which plays a significant role in various diseases, especially cancer. Urological cancers, which account for high male mortality worldwide, pose a persistent challenge due to their incurability and tendency to develop drug resistance. Among the numerous dysregulated biological mechanisms, ER stress is a key factor in the progression and treatment response of these cancers. This review highlights the dual role of aberrant ER stress activation in urologic cancers, affecting both tumor growth and therapeutic outcomes. While ER stress can support tumor growth through pro‐survival autophagy, it primarily inhibits cancer progression via apoptosis and pro‐death autophagy. Interestingly, ER stress can paradoxically aid cancer progression through mechanisms such as exosome‐mediated immune evasion. Additionally, the review examines how pharmacological interventions, particularly with phytochemicals, can stimulate ER stress‐mediated tumor suppression. Key regulators, including PERK, IRE1α, and ATF6, are discussed for their roles in upregulating CHOP levels and triggering apoptosis. In conclusion, a deeper understanding of ER stress in urological cancers not only clarifies the complex interactions between cellular stress and cancer progression but also provides new opportunities for innovative therapeutic strategies.

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Dissociation of NSC606985 induces atypical ER-stress and cell death in prostate cancer cells

Cited by 6 publications

References 62 publications

Anacardic acid induces cell apoptosis of prostatic cancer through autophagy by ER stress/DAPK3/Akt signaling pathway

Anacardic acid induces cell apoptosis of prostatic cancer through autophagy by ER stress/DAPK3/Akt signaling pathway

<p>Statins induce cell apoptosis through a modulation of AKT/FOXO1 pathway in prostate cancer cells</p>

Exploring the dual role of endoplasmic reticulum stress in urological cancers: Implications for tumor progression and cell death interactions

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