Ouabain Induces Apoptotic Cell Death Through Caspase- and Mitochondria-dependent Pathways in Human Osteosarcoma U-2 OS Cells

Chou, Wen Hsiang; Liu, Ko Lin; Shih, Yu‐Lueng; Chuang, Ying Ying; Chou, Jason; Lu, Hsu Feng; Jair, Herng Woei; Lee, Ming Zhe; Au, Man Kuan; Chung, Jing Gung

doi:10.21873/anticanres.12205

Cited by 25 publications

(25 citation statements)

References 27 publications

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“…On the contrary, they conduct the delayed suppression effect on renal cancer and prostate cancer growth via other pathways, including caspase‐3 activation, with migration inhibition. Apoptosis of tumor cells can be induced by the activation of the PARP‐bcl‐2‐caspase 3 pathway, which also is related to mitochondria activity 36, 37, 38. Different urological cancers present different sensitivity and related cytotoxicity by niclosamide and B17 derivative via PARP‐bcl‐2 signal pathway in this study.…”

Section: Discussionmentioning

confidence: 67%

A new niclosamide derivatives‐B17 can inhibit urological cancers growth through apoptosis‐related pathway

Chen

Huang

et al. 2018

Cancer Medicine

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The incidence and mortality rate of urological cancers is increasing yearly. Niclosamide has been repurposed as an anti‐cancer drug in recent years. Synthesized derivative of niclosamide was testified for its anti‐cancer activity in urological cancers. MTT assay was used to measure the cytotoxicity effect of niclosamide and its derivatives in urological cancer cell lines. Migratory ability was monitored by scratch migration assay. Apoptosis and cell cycle changes were analyzed by annexin V and PI staining. The apoptosis‐related signal proteins were evaluated by western blotting. T24 had the best drug sensitivity with the lowest IC 50 in niclosamide and B17 treatment than DU145 and Caki‐1 cells. After niclosamide and B17 treatment, the mitotic cells were decreased, but apoptotic bodies and morphology changes were not prominent in T24, Caki‐1, and DU145 cells. The migratory ability was inhibited in niclosamide treatment than control group on Caki‐1 cells and niclosamide and B17 treatment than control group on DU145 cells. Early apoptosis cells were increased after niclosamide and B17 treatment than control group without cell cycle changes in T24, Caki‐1, and DU145 cells. Programmed cell death was activated majorly through PAPR and bcl‐2 in T24 and caspase‐3 in Caki‐1 cells, respectively. Niclosamide and B17 derivative had good ability in inhibition proliferation and migratory ability in T24, Caki‐1, and DU145 cells without prominent morphology and apoptotic body changes. UCC cells are more sensitive to niclosamide and B17 treatment. Early apoptosis was induced after niclosamide and B17 treatment through different mechanisms in T24, Caki‐1, and DU145 cells.

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Section: Discussionmentioning

confidence: 67%

A new niclosamide derivatives‐B17 can inhibit urological cancers growth through apoptosis‐related pathway

Chen

Huang

et al. 2018

Cancer Medicine

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“…We found that in OSC, blocking Na + /K + -exchanging ATPase with ouabain induced cell death at the later time points (days 7, 10, 14). In a similar study, Chou et al ( 2018 ) investigated the effect of ouabain on apoptotic cell death of human osteosarcoma-derived U-2 OS cells. Based on their finding they suggest that blocking Na + /K + -exchanging ATPase with ouabain induced S-G2/M phase cell-cycle arrest in osteosarcoma cells, which in turn induced apoptotic cell death by activating the caspase-dependent and -independent pathways, accompanied also by mitochondrial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Role of Bioelectricity During Cell Proliferation in Different Cell Types

Bhavsar

Leppik

Oliveira

et al. 2020

Front. Bioeng. Biotechnol.

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Most living organisms possess varying degrees of regenerative capabilities but how these regenerative processes are controlled is still poorly understood. Naturally occurring bioelectric voltages (like V mem) are thought to be playing instructive role in tissue regeneration, as well as embryonic development. The different distribution of ions on the either side of the cell membrane results in intra-and extra-cellular voltage differences, known as membrane potential or V mem. The relationship between V mem and cell physiology is conserved in a wide range of cell types and suggests that V mem regulation is a fundamental control mechanism for regeneration related processes e.g., proliferation and differentiation. In the present study we measured V mem in three different cell types (human osteogenic sarcoma cell line (OSC), rat bone marrow derived mesenchymal stem cells (BM-MSC), and rat dermal fibroblasts) and characterized the relationship between their V mem and proliferation. In order to find out if V mem controls proliferation, or visa-versa, we blocked and then unblocked Na + /K +-exchanging ATPase using ouabain and measured the proliferation. Our results demonstrate that V mem can be pharmacologically manipulated to control proliferation in certain cell types like BM-MSC. Taken together, it is clear that control of bioelectrical properties in non-excitable cells could prove to be potentially a useful tool in regenerative medicine efforts.

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“…In addition, GAS5 promoted the apoptosis of ovarian cancer cells via caspase-3 and caspase-9 upregulation (37). Additionally, the oncogenesis of some cartilage tumors, including chondrosarcoma and chondroblastic osteosarcoma, has exhibited a high correlation with the mitochondrial pathway of apoptosis (38–40). Future studies on these tumors are required to further verify the function of GAS5 in mitochondrial apoptosis, providing that GAS5, as a tumor suppressor, may inhibit tumor growth and proliferation.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA GAS5 promotes apoptosis in primary nucleus pulposus cells derived from the human intervertebral disc via Bcl‑2 downregulation and caspase‑3 upregulation

et al. 2019

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Nucleus pulposus cell (NPC) apoptosis serves an important role in intervertebral disc degeneration (IDD); however, the roles of long noncoding RNAs (lncRNAs) in this process remain unknown. The present study aimed to determine the effects of the lncRNA growth arrest-specific transcript 5 (GAS5) on the apoptosis of primary human NPCs derived from the intervertebral disc, and to investigate the underlying mechanisms. TargetScan was used to predict the lncRNAs targeted by microRNA-155 (miR-155). Then, NPCs were subjected to lentivirus-mediated transduction of miR-155 or GAS5. A human lncRNA and mRNA array was used to screen differentially expressed lncRNAs following miR-155 overexpression. GAS5 and miR-155 expression levels were determined by reverse transcription-quantitative polymerase chain reaction. After GAS5 overexpression, apoptosis was assessed by flow cytometry via Annexin V/propidium iodide staining. Western blotting was employed to determine the expression of apoptosis-associated proteins, including caspase-3 and B cell lymphoma 2 (Bcl-2). TargetScan indicated GAS5 had one binding site for miR-155. Following exogenous transfection of miR-155 mimics, GAS5 expression levels in NPCs were significantly decreased (P<0.05). Interestingly, miR-155 overexpression in NPCs resulted in 721 differentially expressed lncRNAs compared with the negative control group (P<0.05), including 492 and 229 upregulated and downregulated lncRNAs respectively. In addition, 18 transcripts of GAS5 exhibited a downregulated expression profile. GAS5 overexpression in NPCs resulted in enhanced caspase-3 decreased Bcl-2 expression levels; the apoptosis of NPCs was significantly increased (P<0.05). The results of the present study revealed that overexpression of lncRNA GAS5 may promotes NPC apoptosis via Bcl-2 downregulation and caspase-3 upregulation, which may be associated with miR-155. The results of the present study suggest that lncRNA GAS5-silenced NPCs, or lentivirus-mediated lncRNA GAS5 knockdown may be precise and effective therapeutic strategies in the treatment of IDD.

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Ouabain Induces Apoptotic Cell Death Through Caspase- and Mitochondria-dependent Pathways in Human Osteosarcoma U-2 OS Cells

Abstract: Our findings provide important insight into the cytotoxic effects of ouabain on U-2 OS cells, in vitro, which are mediated at least partly via cell apoptosis induction.

Cited by 25 publications

References 27 publications

A new niclosamide derivatives‐B17 can inhibit urological cancers growth through apoptosis‐related pathway

A new niclosamide derivatives‐B17 can inhibit urological cancers growth through apoptosis‐related pathway

Role of Bioelectricity During Cell Proliferation in Different Cell Types

Long noncoding RNA GAS5 promotes apoptosis in primary nucleus pulposus cells derived from the human intervertebral disc via Bcl‑2 downregulation and caspase‑3 upregulation

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