Retigeric acid B-induced mitophagy by oxidative stress attenuates cell death against prostate cancer cells in vitro

Liu, Yongqing; Ji, Yuan; Li, Xian-zhe; Tian, Keli; Young, Charles Y.F.; Lou, Hongxiang; Yuan, Huipin

doi:10.1038/aps.2013.68

Cited by 21 publications

(12 citation statements)

References 31 publications

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“…Recent work by Zhang et al has confirmed the importance of PGCCs in therapy resistance and ovarian cancer progression [ 25 , 75 ]. In contrast with polyploidization, we supposed that mitophagy is more general principle of coping with cell stress in immortalized cells, which is in accordance with other studies [ 76 – 78 ].…”

Section: Discussionsupporting

confidence: 91%

Oxidative Stress Resistance in Metastatic Prostate Cancer: Renewal by Self-Eating

et al. 2015

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Resistant cancer phenotype is a key obstacle in the successful therapy of prostate cancer. The primary aim of our study was to explore resistance mechanisms in the advanced type of prostate cancer cells (PC-3) and to clarify the role of autophagy in these processes. We performed time-lapse experiment (48 hours) with ROS generating plumbagin by using multimodal holographic microscope. Furthermore, we also performed the flow-cytometric analysis and the qRT-PCR gene expression analysis at 12 selected time points. TEM and confocal microscopy were used to verify the results. We found out that autophagy (namely mitophagy) is an important resistance mechanism. The major ROS producing mitochondria were coated by an autophagic membrane derived from endoplasmic reticulum and degraded. According to our results, increasing ROS resistance may be also accompanied by increased average cell size and polyploidization, which seems to be key resistance mechanism when connected with an escape from senescence. Many different types of cell-cell interactions were recorded including entosis, vesicular transfer, eating of dead or dying cells, and engulfment and cannibalism of living cells. Entosis was disclosed as a possible mechanism of polyploidization and enabled the long-term survival of cancer cells. Significantly reduced cell motility was found after the plumbagin treatment. We also found an extensive induction of pluripotency genes expression (NANOG, SOX2, and POU5F1) at the time-point of 20 hours. We suppose, that overexpression of pluripotency genes in the portion of prostate tumour cell population exposed to ROS leads to higher developmental plasticity and capability to faster respond to changes in the extracellular environment that could ultimately lead to an alteration of cell fate.

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Section: Discussionsupporting

confidence: 91%

Oxidative Stress Resistance in Metastatic Prostate Cancer: Renewal by Self-Eating

et al. 2015

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“…6,29 Similarly to antimycin A, a diverse range of chemicals, including sodium selenite, diquat, retigeric acid B and paraquat have been reported to trigger mitophagy in response to elevated levels of oxidative stress ( Table 1). 4,20,[35][36][37] …”

Section: Mitochondrial Toxinsmentioning

confidence: 99%

The pharmacological regulation of cellular mitophagy

2017

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Small molecules are pharmacological tools of considerable value in dissecting complex biological processes and identifying potential therapeutic interventions.Recently, the cellular quality control process of mitophagy attracted considerable research interest, however, the limited availability of suitable chemical probes restricted our understanding of the molecular mechanisms involved.Current approaches to initiate mitophagy include acute dissipation of the mitochondrial membrane potential (ΔΨm) by mitochondrial uncouplers (e.g. FCCP/CCCP), or the use of Antimycin A/Oligomycin to impair respiration. Both approaches impair mitochondrial homeostasis, and therefore limit the scope for dissection of subtle, bio-energy related regulatory phenomena.Recently, novel mitophagy activators acting independently of the respiration collapse have been reported, offering new opportunities to understand the process and potential for therapeutic exploitation.We have therefore summarized the current status of mitophagy modulators and analyzed the available chemical tools, commenting on their advantages, limitations and current applications.

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“…Inactivation of the PI3K/Akt pathway prevents the translocation of damageregulated autophagy modulator to the mitochondria and induces apoptosis in hepatocellular carcinoma cells by the mediation of mitophagy (41). Furthermore, inhibition of the PI3K/Akt/mTOR signaling pathway is accompanied by autophagy and mitophagy in human glioblastoma cells, glioblastoma stem cells and human prostate cancer (42,43). In the present study, the results indicated that 17β-E2 regulated mitophagy in INS-1 cells through the GPER/PI3K/Akt pathway.…”

Section: Discussionmentioning

confidence: 99%

17β-estradiol protects INS-1 insulinoma cells from mitophagy via G protein-coupled estrogen receptors and the PI3K/Akt signaling pathway

2018

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17β-estradiol (17β-E2) is a steroid hormone that is known to exert effects on blood glucose homeostasis. The G protein‑coupled estrogen receptor (GPER) has been identified as a non-genomic estrogenic receptor, and is involved in numerous physiological processes, including cell survival, energy provision and metabolism. 17β-E2 may decrease apoptosis by binding to the GPER. The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is involved in physiological and pathological functions such as autophagy. The purpose of the present study was to investigate the role of the PI3K/Akt signaling pathway in the mediation of the effects of GPERs, and the effects of 17β-E2 on mitophagy in INS-1 cells, a rat insulin‑secreting β-cell line. In vitro, INS-1 cells were treated with different concentrations of 17β-E2 with and without pretreatment with a GPER antagonist (G15) or PI3K antagonist (LY294002) and compared with a negative control. An immunofluorescence assay demonstrated that GPERs are expressed in INS-1 cells. Western blot assays demonstrated that 17β-E2 increased GPER levels and the phosphorylation of Akt. Transmission electronic microscopy revealed that 17β-E2 reduced the formation of mitophagosomes and autophagosomes in INS-1 cells. An immunofluorescence staining assay indicated that the co-localization of translocase of mitochondrial outer membrane complex 20 (TOM20) with lysosomal-associated membrane protein 2 (LAMP2) was decreased in INS-1 cells treated with 17β-E2 alone. Western blotting demonstrated that 17β-E2 reduced the protein levels of activated microtubule-associated protein-1 light chain 3, and increased those of TOM20 and mitochondrial heat-shock protein 60. Notably, the protective effects of 17β-E2 were significantly diminished by G15 or LY294002. In conclusion, the present study suggests that 17β-E2 activates the PI3K/Akt pathway via the GPER in INS-1 cells. Furthermore, 17β-E2 may be involved in mitophagy by the regulating the GPER/PI3K/Akt pathway.

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Retigeric acid B-induced mitophagy by oxidative stress attenuates cell death against prostate cancer cells in vitro

Cited by 21 publications

References 31 publications

Oxidative Stress Resistance in Metastatic Prostate Cancer: Renewal by Self-Eating

Oxidative Stress Resistance in Metastatic Prostate Cancer: Renewal by Self-Eating

The pharmacological regulation of cellular mitophagy

17β-estradiol protects INS-1 insulinoma cells from mitophagy via G protein-coupled estrogen receptors and the PI3K/Akt signaling pathway

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