Effective Killing of Leukemia Cells by the Natural Product OSW-1 through Disruption of Cellular Calcium Homeostasis

Garcı́a-Prieto, Celia; Ahmed, Kausar Begam Riaz; Zhao, Chen; Zhou, Yan; Hammoudi, Naima; Kang, Ying; Lou, Changgang; Mei, Yan; Jin, Zhendong; Huang, Peng

doi:10.1074/jbc.m112.384776

Cited by 54 publications

(45 citation statements)

References 60 publications

(66 reference statements)

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“…Several studies have also shown that OSW-1 can induce calcium-or caspase-8-dependent cleavage of Bcl-2-mediated apoptosis (34,35). Based on this study, we speculated that OSW-1 is capable of inducing apoptosis in LoVo cells.…”

Section: Apoptosis Is the Main Cause Of Lovo Cell Death After Exposurmentioning

confidence: 87%

“…Previous studies have suggested that apoptosis, a universal cellular process, is the mechanism of many anticancer drugs (43)(44)(45)(46). Several studies have reported that OSW-1 can induce calcium-dependent apoptosis by damaging the mitochondrial membrane and disrupting cellular homeostasis or caspase-8-dependent cleavage of Bcl-2 in leukemia and Chinese hamster ovary (CHO) cells in vitro, respectively (34,35). We believe that apoptosis is a dominant pattern in the OSW-1-treated group based on the Annexin V assay, which was verified by the TUNEL assay in vitro.…”

Section: Discussionmentioning

confidence: 99%

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Effective cytotoxic activity of OSW-1 on colon cancer by inducing apoptosis in vitro and in vivo

et al. 2017

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Abstract. As a natural compound, Ornithogalum caudatumAit is primarily used as an anti-inflammatory and antitumor agent in Chinese folk medicine. In 1992, OSW-1 was isolated from this compound, which is a new member of cholestane saponin family. In numerous recent studies, OSW-1 has been shown to have powerful cytotoxic anticancer effects against various malignant cells. However, the therapeutic efficacy of OSW-1 on colon cancer and the underlying mechanism are not understood. To explore the mechanism underlying OSW-1 in antitumor therapy, a therapeutic function analysis of OSW-1 on colon cancer was performed in vitro and in vivo. It was shown that with low toxicity on normal colonic cells, OSW-1 suppresses colon cancer cells in vitro and this inhibition was via the intrinsic apoptotic pathway, which increased cellular calcium, changed mitochondrial membrane potential, disrupted mitochondrial morphology, and led to the release of cytochrome c and the activation of caspase-3. Furthermore, in a nude mouse model, OSW-1 had a powerful effect on suppressing colon tumor proliferation without significant side effects through the apoptosis pathway. Taken together, these results demonstrate that OSW-1 is a potential drug for colon cancer treatment.

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Section: Apoptosis Is the Main Cause Of Lovo Cell Death After Exposurmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Effective cytotoxic activity of OSW-1 on colon cancer by inducing apoptosis in vitro and in vivo

et al. 2017

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“…For instance, cephalostatin promotes DNA fragmentation, caspase 3 activation, JNK phosphorylation, and PARP cleavage (33,34) but induces mitochondria release of Smac/Diablo (but not cytochrome c), endoplasmic reticulum stress and caspase 9 activation by an apoptosome-independent mechanism (33,35). Some of these events are evident in ORP4-depleted cells, suggesting that cephalostatin and ORPphilins could inactivate an ORP4-dependent cell survival pathway in cancer cells (36). Although ORP4 is unique in the mammalian OSBP family for its essential role in a cell survival pathway, further research is required to more precisely define its cell-specific functions that support proliferation.…”

Section: Discussionmentioning

confidence: 99%

Oxysterol-binding Protein (OSBP)-related Protein 4 (ORP4) Is Essential for Cell Proliferation and Survival

Charman¹,

Colbourne²,

Pietrangelo³

et al. 2014

Journal of Biological Chemistry

118

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Background:The function of oxysterol-binding protein-related protein (ORP4) is unknown. Results: Silencing ORP4L or all ORP4 isoforms triggers growth arrest and apoptosis, which is suppressed by H-Ras and involves the C-terminal lipid binding domain. Conclusion: ORP4 is a sterol and PI-4P-binding protein required for survival and proliferation of immortalized and transformed cells. Significance: This is the first study to identify a mammalian ORP with growth regulatory activity.

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“…The TCA cycledependent production of ATP and metabolic intermediates are required for the synthesis of fatty acids and nucleotides (Boroughs & Deberardinis, 2015). Oncogenes or tumour suppressors can promote cell survival or induce death by modifying uniplex activity (Garcia-Prieto et al, 2013;. Reduced mitochondrial Ca 2+ uptake has been demonstrated to reduce O 2 consumption and ATP level, thus activate AMP-activated protein kinase-dependent prosurvival macro-autophagy (Cárdenas et al, 2010).…”

Section: Reprogramming Of Uniplex-mediated Calcium Signalling In Camentioning

confidence: 99%

“…Down-regulation or inhibition of MCU increases proliferation and renders cells resistant to apoptosis by diminishing Ca 2+ entry into mitochondria. Oncogenes or tumour suppressors can promote cell survival or induce death by modifying uniplex activity (Garcia-Prieto et al, 2013;. Here, we summarize the data available on the deregulation of uniplex-mediated Ca 2+ signalling in cancer (Table 1).…”

Section: Reprogramming Of Uniplex-mediated Calcium Signalling In Camentioning

confidence: 99%

Progress in understanding mitochondrial calcium uniporter complex‐mediated calcium signalling: A potential target for cancer treatment

Cui

Yang

et al. 2019

British J Pharmacology

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Due to its Ca 2+ buffering capacity, the mitochondrion is one of the most important intracellular organelles in regulating Ca 2+ dynamic oscillation. Mitochondrial calcium uniporter (MCU) is the primary mediator of Ca 2+ influx into mitochondria, manipulating cell energy metabolism, ROS production, and programmed cell death, all of which are critical for carcinogenesis. The understanding of the uniporter complex was significantly boosted by recent groundbreaking discoveries that identified the uniporter pore-forming subunit MCU and its regulatory molecules, including MCU-dominant negative β subunit (MCUb), essential MCU regulator (EMRE), MCU regulator 1 (MCUR1), mitochondrial calcium uptake (MICU) 1, MICU2, and MICU3. These provide the means and molecular platform to investigate MCU complex (uniplex)-mediated impaired Ca 2+ signalling in physiology and pathology. This review aims to summarize the progress of the understanding regulatory mechanisms of uniplex, roles of uniplex-mediated Ca 2+ signalling in cancer, and potential pharmacological inhibitors of MCU.

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Effective Killing of Leukemia Cells by the Natural Product OSW-1 through Disruption of Cellular Calcium Homeostasis

Cited by 54 publications

References 60 publications

Effective cytotoxic activity of OSW-1 on colon cancer by inducing apoptosis in vitro and in vivo

Effective cytotoxic activity of OSW-1 on colon cancer by inducing apoptosis in vitro and in vivo

Oxysterol-binding Protein (OSBP)-related Protein 4 (ORP4) Is Essential for Cell Proliferation and Survival

Progress in understanding mitochondrial calcium uniporter complex‐mediated calcium signalling: A potential target for cancer treatment

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