Monensin Induces PC-3 Prostate Cancer Cell Apoptosis via ROS Production and Ca2+ Homeostasis Disruption

Kim, Sanghun; Kim, Kwang S.; Yu, Sun‐Nyoung; Park, Sul-Gi; Yu, Hak Sun; Seo, Young‐Kyo; Ahn, Soon‐Cheol

doi:10.21873/anticanres.11168

Cited by 39 publications

(32 citation statements)

References 28 publications

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“…Being an ionophore, monensin also alters the concentration of cations inside the cells. This has been demonstrated in prostate cancer cell lines, where intracellular Ca+ levels were reduced in the presence of the drug and this was the primary mechanism leading to cell cycle arrest and apoptosis [79].…”

Section: Discussionmentioning

confidence: 88%

A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin

Pádua

Barros

Amaral

et al. 2020

Cancers

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Gastric cancer remains a serious health burden with few therapeutic options. Therefore, the recognition of cancer stem cells (CSCs) as seeds of the tumorigenic process makes them a prime therapeutic target. Knowing that the transcription factors SOX2 and OCT4 promote stemness, our approach was to isolate stem-like cells in human gastric cancer cell lines using a traceable reporter system based on SOX2/OCT4 activity (SORE6-GFP). Cells transduced with the SORE6-GFP reporter system were sorted into SORE6+ and SORE6– cell populations, and their biological behavior characterized. SORE6+ cells were enriched for SOX2 and exhibited CSC features, including a greater ability to proliferate and form gastrospheres in non-adherent conditions, a larger in vivo tumor initiating capability, and increased resistance to 5-fluorouracil (5-FU) treatment. The overexpression and knockdown of SOX2 revealed a crucial role of SOX2 in cell proliferation and drug resistance. By combining the reporter system with a high-throughput screening of pharmacologically active small molecules we identified monensin, an ionophore antibiotic, displaying selective toxicity to SORE6+ cells. The ability of SORE6-GFP reporter system to recognize cancer stem-like cells facilitates our understanding of gastric CSC biology and serves as a platform for the identification of powerful therapeutics for targeting gastric CSCs.

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Section: Discussionmentioning

confidence: 88%

A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin

Pádua

Barros

Amaral

et al. 2020

Cancers

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“…It was reported that PC-3 cells undergo apoptosis when exposed to other compounds like the chemotherapeutic agents salinomycin ( 34 ) and monensin ( 35 ), associated with exposure of PS. Also, other studies with the osteosarcoma MG-63 cell line showed apoptosis induction through exposure of PS by treatment with berberine ( 36 ) and ascorbic acid ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Bovine Milk Lactoferrin Selectively Kills Highly Metastatic Prostate Cancer PC-3 and Osteosarcoma MG-63 Cells In Vitro

et al. 2018

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Prostate cancer and osteosarcoma are the second most common type of cancer affecting men and the fifth most common malignancy among adolescents, respectively. The use of non-toxic natural or natural-derived products has been one of the current strategies for cancer therapy, owing to the reduced risks of induced-chemoresistance development and the absence of secondary effects. In this perspective, lactoferrin (Lf), a natural protein derived from milk, emerges as a promising anticancer agent due to its well-recognized cytotoxicity and anti-metastatic activity. Here, we aimed to ascertain the potential activity of bovine Lf (bLf) against highly metastatic cancer cells. The bLf effect on prostate PC-3 and osteosarcoma MG-63 cell lines, both displaying plasmalemmal V-ATPase, was studied and compared with the breast cancer MDA-MB-231 and the non-tumorigenic BJ-5ta cell lines. Cell proliferation, cell death, intracellular pH, lysosomal acidification, and extracellular acidification rate were evaluated. Results show that bLf inhibits proliferation, induces apoptosis, intracellular acidification, and perturbs lysosomal acidification only in highly metastatic cancer cell lines. By contrast, BJ-5ta cells are insensitive to bLf. Overall, our results establish a common mechanism of action of bLf against highly metastatic cancer cells exhibiting plasmalemmal V-ATPase. This study opens promising perspectives for further research on the anticancer role of Lf, which ultimately will contribute to its safer and more rational application in the human therapy of these life-threatening cancers.

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“… 7 , 14 Intrinsic levels of ROS are frequently elevated in cancer cells, typically arising from mitochondrial dysfunction and the higher metabolic activity associated with tumor proliferation and metastasis. 15 However, further oxidative stress is known to cause cell cycle arrest and apoptosis, 16 − 19 which therefore presents a novel chemotherapeutic target that could render selectivity toward cancer cells. 20 In this work, we compare the antiproliferative activity of these previously reported classes of Os(II) compounds, 10 , 21 their ability to generate reactive oxygen species (ROS) in both cancer cells and in vivo , as well as their remarkable selectivity and potential for circumventing Pt-resistance.…”

Section: Introductionmentioning

confidence: 99%

In Vivo Selectivity and Localization of Reactive Oxygen Species (ROS) Induction by Osmium Anticancer Complexes That Circumvent Platinum Resistance

et al. 2018

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Platinum drugs are widely used for cancer treatment. Other precious metals are promising, but their clinical progress depends on achieving different mechanisms of action to overcome Pt-resistance. Here, we evaluate 13 organo-Os complexes: 16-electron sulfonyl-diamine catalysts [(η6-arene)Os(N,N′)], and 18-electron phenylazopyridine complexes [(η6-arene)Os(N,N’)Cl/I]+ (arene = p-cymene, biphenyl, or terphenyl). Their antiproliferative activity does not depend on p21 or p53 status, unlike cisplatin, and their selective potency toward cancer cells involves the generation of reactive oxygen species. Evidence of such a mechanism of action has been found both in vitro and in vivo. This work appears to provide the first study of osmium complexes in the zebrafish model, which has been shown to closely model toxicity in humans. A fluorescent osmium complex, derived from a lead compound, was employed to confirm internalization of the complex, visualize in vivo distribution, and confirm colocalization with reactive oxygen species generated in zebrafish.

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Monensin Induces PC-3 Prostate Cancer Cell Apoptosis via ROS Production and Ca2+ Homeostasis Disruption

Abstract: Monensin induces cell-cycle arrest and apoptosis through regulation of cell cycle- and apoptosis-related proteins, resulting in induction of mitochondrial ROS- and Ca-dependent apoptosis, respectively.

Cited by 39 publications

References 28 publications

A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin

A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin

Bovine Milk Lactoferrin Selectively Kills Highly Metastatic Prostate Cancer PC-3 and Osteosarcoma MG-63 Cells In Vitro

In Vivo Selectivity and Localization of Reactive Oxygen Species (ROS) Induction by Osmium Anticancer Complexes That Circumvent Platinum Resistance

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