p62 Suppressed VK3-induced Oxidative Damage Through Keap1/Nrf2 Pathway In Human Ovarian Cancer Cells

Xia, Meihui; Yan, Xiaoyu; Zhou, Lei; Xu, Long; Zhang, Lichao; Huiuk, Yi; Su, Jing

doi:10.7150/jca.34423

Cited by 26 publications

(18 citation statements)

References 40 publications

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“…Mitochondrial ROS signalling is also considered a valuable target since the imbalance between ROS production and ROS detoxification constitutes the pivotal molecular route contributing to aberrant proliferation and tumour cell survival in several types of cancer. Vitamin K3 (VK3) has the potential to be developed as an antitumour agent since it induces apoptosis by increasing the generation of ROS in ovarian cancer cells [111] . However, many cancer cells benefit from mROS generation through its effects on redox signalling; thus, refined strategies that allow for the specific modulation of mROS must be conceived.…”

Section: Mitochondria As Promising Targets For Cancer Therapymentioning

confidence: 99%

Cancer metabolism and mitochondria: Finding novel mechanisms to fight tumours

et al. 2020

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Mitochondria are dynamic organelles that have essential metabolic activity and are regarded as signalling hubs with biosynthetic, bioenergetics and signalling functions that orchestrate key biological pathways. However, mitochondria can influence all processes linked to oncogenesis, starting from malignant transformation to metastatic dissemination. In this review, we describe how alterations in the mitochondrial metabolic status contribute to the acquisition of typical malignant traits, discussing the most recent discoveries and the many unanswered questions. We also highlight that expanding our understanding of mitochondrial regulation and function mechanisms in the context of cancer cell metabolism could be an important task in biomedical research, thus offering the possibility of targeting mitochondria for the treatment of cancer.

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Section: Mitochondria As Promising Targets For Cancer Therapymentioning

confidence: 99%

Cancer metabolism and mitochondria: Finding novel mechanisms to fight tumours

et al. 2020

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“…Recent studies have reported that Nrf2 could be activated by AMP-activated protein kinase (AMPK) and modulate autophagy-related genes (e.g., p62, Beclin, and LC3B-1/2) to participate in the alleviation of oxidative stress in mammalian cells [ 22 ]. Autophagy-related protein p62 can inhibit Nrf2 degradation and promote Nrf2 stability and nuclear translocation by interfering with Keap1-Nrf2 interaction to participate in the cellular antioxidative stress response [ 23 ]. However, whether ZnLA could protect against oxidative stress by modulating AMPK-Nrf2 activation and autophagy signals is still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

The Associated Regulatory Mechanisms of Zinc Lactate in Redox Balance and Mitochondrial Function of Intestinal Porcine Epithelial Cells

Tang

Long

et al. 2020

Oxidative Medicine and Cellular Longevity

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Zinc lactate (ZnLA) is a new organic zinc salt which has antioxidant properties in mammals and can improve intestinal function. This study explored the effects of ZnLA and ZnSO4 on cell proliferation, Zn transport, antioxidant capacity, mitochondrial function, and their underlying molecular mechanisms in intestinal porcine epithelial cells (IPEC-J2). The results showed that addition of ZnLA promoted cell proliferation, inhibited cell apoptosis and IL-6 secretion, and upregulated the mRNA expression and concentration of MT-2B, ZNT-1, and CRIP, as well as affected the gene expression and activity of oxidation or antioxidant enzymes (e.g., CuZnSOD, CAT, and Gpx1, GSH-PX, LDH, and MDA), compared to ZnSO4 or control. Compared with the control, ZnLA treatment had no significant effect on mitochondrial membrane potential, whereas it markedly increased the mitochondrial basal OCR, nonmitochondrial respiratory capacity, and mitochondrial proton leakage and reduced spare respiratory capacity and mitochondrial reactive oxygen (ROS) production in IPEC-J2 cells. Furthermore, ZnLA treatment increased the protein expression of Nrf2 and phosphorylated AMPK, but reduced Keap1 and p62 protein expression and autophagy-related genes LC3B-1 and Beclin mRNA abundance. Under H2O2-induced oxidative stress conditions, ZnLA supplementation markedly reduced cell apoptosis and mitochondrial ROS levels in IPEC-J2 cells. Moreover, ZnLA administration increased the protein expression of Nrf2 and decreased the protein expression of caspase-3, Keap1, and p62 in H2O2-induced IPEC-J2 cells. In addition, when the activity of AMPK was inhibited by Compound C, ZnLA supplementation did not increase the protein expression of nuclear Nrf2, but when Compound C was removed, the activities of AMPK and Nfr2 were both increased by ZnLA treatment. Our results indicated that ZnLA could improve the antioxidant capacity and mitochondrial function in IPEC-J2 cells by activating the AMPK-Nrf2-p62 pathway under normal or oxidative stress conditions. Our novel finding also suggested that ZnLA, as a new feed additive for piglets, has the potential to be an alternative for ZnSO4.

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“…Nuclear factor E2-related factor 2 (Nrf2) is a key transcription factor involving in maintaining cell redox homeostasis 89 , and HO-1 is one of the most important regulatory products. It is a bZIP transcription factor 10 . Under resting conditions, Nrf2 binds to kelch-like ECH-related protein 1 (keap1) and form a Keap1-Nrf2 complex 90 .…”

Section: Regulation Mechanism Of Ho-1 Expressionmentioning

confidence: 99%

“…The complex will be degraded by ubiquitous proteasome and exist in the cytoplasm in an inactive state. However, oxidative stress induces the modification of cysteine residues in Keap1, causing Nrf2 to dissociate from the complex and increase the translocation of nucleus 10 . Within the nucleus, it binds to the antioxidant-responsive element (ARE) in target gene promoters and form the Nrf2-ARE signaling pathway 90 , activating the transcription of its downstream target genes, such as HO-1 and NADPH quinone dehydrogenase 1 (NQO1), protecting cells from oxidative damage and participating in maintaining redox homeostasis 24 , 42 , 56 .…”

Section: Regulation Mechanism Of Ho-1 Expressionmentioning

confidence: 99%

Heme oxygenase 1: a novel oncogene in multiple gynecological cancers

Lu¹,

Abudukeyoumu²,

Zhang³

et al. 2021

Int. J. Biol. Sci.

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Heme oxygenase 1 (HO-1), also known as heat shock protein 32 (HSP32), is a stress-inducible enzyme. In the past, it was believed to participate in maintaining cell homeostasis, reducing oxidative stress damage and exerting anti-apoptotic effects. When exposed to noxious stimulation, the expression of HO-1 in the body will increase, antagonizing these oxidative stresses and protecting our bodies. Recently, many studies showed that HO-1 was also highly-expressed in multiple gynecological cancers (such as ovarian cancer, cervical cancer and endometrial cancer), suggesting that it should be closely related to cell proliferation, metastasis, immune regulation and angiogenesis as an oncogene. This review summarizes the different effects of HO-1 under normal and diseased conditions with a brief discussion of its implications on the diagnosis and treatment of gynecological cancers, aiming to provide a new clue for prevention and treatment of diseases.

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p62 Suppressed VK3-induced Oxidative Damage Through Keap1/Nrf2 Pathway In Human Ovarian Cancer Cells

Cited by 26 publications

References 40 publications

Cancer metabolism and mitochondria: Finding novel mechanisms to fight tumours

Cancer metabolism and mitochondria: Finding novel mechanisms to fight tumours

The Associated Regulatory Mechanisms of Zinc Lactate in Redox Balance and Mitochondrial Function of Intestinal Porcine Epithelial Cells

Heme oxygenase 1: a novel oncogene in multiple gynecological cancers

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