ROS Induced by KillerRed Targeting Mitochondria (mtKR) Enhances Apoptosis Caused by Radiation via Cyt c/Caspase-3 Pathway

Li, Xin; Fang, Fang; Gao, Ying; Tang, Geng; Xu, Weiqiang; Wang, Yihan; Kong, Ruoxian; Tuyihong, Ayixianguli; Wang, Zhicheng

doi:10.1155/2019/4528616

Cited by 46 publications

(42 citation statements)

References 46 publications

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“…Moreover, the mechanisms involved in photoactivated NBC cell death leading to free radical apoptosis of CSCs remain unknown, as cell death may be caused by distinct, but overlapping, signaling pathways that respond to different stimuli [78]. Cell death pathways and signaling mechanisms can be studied by numerous metabolic studies, including RT-PCR caspase signaling identification, Cytochrome C and ROS identification and DNA destruction [79]. The aforementioned recommendations will aim to address any limitations observed in this report.…”

Section: Discussionmentioning

confidence: 99%

Effective Gold Nanoparticle-Antibody-Mediated Drug Delivery for Photodynamic Therapy of Lung Cancer Stem Cells

Crous

Abrahamse

2020

IJMS

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Cancer stem cells (CSCs) are a leading contributor to lung cancer mortality rates. CSCs are responsible for tumor growth and recurrence through inhibition of drug-induced cell death, decreasing the effect of traditional cancer therapy and photodynamic therapy (PDT). PDT can be improved to successfully treat lung cancer by using gold nanoparticles (AuNPs), due to their size and shape, which have been shown to facilitate drug delivery and retention, along with the targeted antibody (Ab) mediated selection of CSCs. In this study, a nanobioconjugate (NBC) was constructed, using a photosensitizer (PS) (AlPcS4Cl), AuNPs and Abs. The NBC was characterized, using spectroscopy techniques. Photodynamic effects of the NBC on lung CSCs was evaluated, using biochemical assays 24 h post-irradiation, in order to establish its anticancer effect. Results showed successful conjugation of the nanocomposite. Localization of the NBC was seen to be in integral organelles involved in cell homeostasis. Biochemical responses of lung CSCs treated using AlPcS4Cl-AuNP and AlPcS4Cl-AuNP-Ab showed significant cell toxicity and cell death, compared to free AlPcS4Cl. The PDT effects were enhanced when using the NBC, showing significant lung CSC destruction to the point of eradication.

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Section: Discussionmentioning

confidence: 99%

Effective Gold Nanoparticle-Antibody-Mediated Drug Delivery for Photodynamic Therapy of Lung Cancer Stem Cells

Crous

Abrahamse

2020

IJMS

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“…Bcl-2 is an anti-apoptotic protein, which belongs to the Bcl-2 family of proteins, and is considered a classical biomarker of the mitochondrial pathway of apoptosis (27). In apoptosis, external stimuli, such as cytotoxic agents, could result in mitochondrial dysfunction, and then result in the release of pro-apoptotic protein Cyt c and activation of caspases to induce apoptosis (28). Previous studies demonstrated that the dissociation of the Bcl-2/Bax complex can lead to the release of Cyto C (29,30).…”

Section: Discussionmentioning

confidence: 99%

miR‑222 induces apoptosis in human intervertebral disc nucleus pulposus cells by targeting Bcl‑2

Wang

Zhang

et al. 2019

Mol Med Report

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intervertebral disc degeneration (idd) is characterized by abnormal induction of apoptosis in intervertebral disc nucleus pulposus (nP) cells. Previous studies indicated that mir-222 was upregulated in patients with rheumatoid arthritis. However, the effects of mir-222 in idd remain unclear. The present study aimed to demonstrate the role of mir-222 in nP cells. The levels of mir-222 in patients with idd were measured by reverse transcription-quantitative Pcr. cell counting Kit-8 and western blotting assays were used to detect cell proliferation and apoptosis-associated protein levels, respectively. in addition, luciferase reporter assays were performed to validate the predicted target genes of miR-222. miR-222 was significantly upregulated in patients with idd. overexpression of mir-222 inhibited cell proliferation and induced cell apoptosis. Moreover, overexpression of mir-222 resulted in an upregulation in the levels of Bax and cleaved caspase 3, and a downregulation in the levels of Bcl-2 in nP cells. The luciferase reporter assays demonstrated that Bcl-2 is a target of mir-222. Furthermore, overexpression of mir-222 increased the levels of cytochrome c, apoptotic protease activating factor-1 and cleaved caspase 9 in nP cells. conversely, downregulation of mir-222 could promote the proliferation of nP cells. The present data demonstrated that mir-222 induced apoptosis in nP cells by directly targeting Bcl-2. Therefore, mir-222 may act as a potential therapeutic target for the treatment of idd.

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“…The genes and their PPI networks highlight their involvement in cell cycle arrest upon detection of DNA damage, affecting DNA replication and repair. During course of DDR, ROS from radiation seems to promote mitochondrial-induced apoptosis [61]. Further, a constant but varying amount of inflammatory responses due to tissue injury (normal and tumor) appears to trigger ROS-induced mitochondrial oxidation [62], which exacerbates local inflammation in nearby tissues and propagates this DNA repair-inflammation stress cycle.…”

Section: Discussionmentioning

confidence: 99%

Genetically-regulated transcriptomics & copy number variation of proctitis points to altered mitochondrial and DNA repair mechanisms in individuals of European ancestry

et al. 2020

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Background Proctitis is an inflammation of the rectum and may be induced by radiation treatment for cancer. The genetic heritability of developing radiotoxicity and prior role of genetic variants as being associated with side-effects of radiotherapy necessitates further investigation for underlying molecular mechanisms. In this study, we investigated gene expression regulated by genetic variants, and copy number variation in prostate cancer survivors with radiotoxicity. Methods We investigated proctitis as a radiotoxic endpoint in prostate cancer patients who received radiotherapy (n = 222). We analyzed the copy number variation and genetically regulated gene expression profiles of whole-blood and prostate tissue associated with proctitis. The SNP and copy number data were genotyped on Affymetrix® Genome-wide Human SNP Array 6.0. Following QC measures, the genotypes were used to obtain gene expression by leveraging GTEx, a reference dataset for gene expression association based on genotype and RNA-seq information for prostate (n = 132) and whole-blood tissue (n = 369). Results In prostate tissue, 62 genes were significantly associated with proctitis, and 98 genes in whole-blood tissue. Six genes - CABLES2, ATP6AP1L, IFIT5, ATRIP, TELO2, and PARD6G were common to both tissues. The copy number analysis identified seven regions associated with proctitis, one of which (ALG1L2) was also associated with proctitis based on transcriptomic profiles in the whole-blood tissue. The genes identified via transcriptomics and copy number variation association were further investigated for enriched pathways and gene ontology. Some of the enriched processes were DNA repair, mitochondrial apoptosis regulation, cell-to-cell signaling interaction processes for renal and urological system, and organismal injury. Conclusions We report gene expression changes based on genetic polymorphisms. Integrating gene-network information identified these genes to relate to canonical DNA repair genes and processes. This investigation highlights genes involved in DNA repair processes and mitochondrial malfunction possibly via inflammation. Therefore, it is suggested that larger studies will provide more power to infer the extent of underlying genetic contribution for an individual’s susceptibility to developing radiotoxicity.

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ROS Induced by KillerRed Targeting Mitochondria (mtKR) Enhances Apoptosis Caused by Radiation via Cyt c/Caspase-3 Pathway

Cited by 46 publications

References 46 publications

Effective Gold Nanoparticle-Antibody-Mediated Drug Delivery for Photodynamic Therapy of Lung Cancer Stem Cells

Effective Gold Nanoparticle-Antibody-Mediated Drug Delivery for Photodynamic Therapy of Lung Cancer Stem Cells

miR‑222 induces apoptosis in human intervertebral disc nucleus pulposus cells by targeting Bcl‑2

Genetically-regulated transcriptomics & copy number variation of proctitis points to altered mitochondrial and DNA repair mechanisms in individuals of European ancestry

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