Salinomycin inhibits proliferation and induces apoptosis of human nasopharyngeal carcinoma cell in vitro and suppresses tumor growth in vivo

Wu, Danxin; Zhang, Yu; Huang, Jie; Fan, Zirong; Shi, Fengrong; Wang, Senming

doi:10.1016/j.bbrc.2013.12.032

Cited by 25 publications

(12 citation statements)

References 39 publications

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“…Salinomycin has recently been shown to inhibit breast and prostate cancer cell proliferation and induce apoptosis, targeting Wnt signaling by decreased LRP5/6 expression, but also by targeting mTORC (Lu and Li, 2014), suggesting it may function in targeting multiple pathways. Salinomycin has also been shown to have anti-tumorigenic effects in hepatocellular carcinoma, osteosarcoma, gastric cancer, NSCLC and nasopharygeal carcinoma; studies suggest that is specifically targets CSCs by inhibiting cell proliferation, inducing apoptosis and limiting cell migration (Arafat et al, 2013; Mao et al, 2014; Tang et al, 2011; Wang et al, 2012a; Wu et al, 2014). COX-2 inhibitors may target the Wnt pathway by inhibiting prostaglandin E2 (PGE 2 ), the product of COX-2, which acts to phosphorylate GSK-3 (Figure 1 [Fujino et al, 2002]).…”

Section: Targeting the Wnt Pathwaymentioning

confidence: 99%

Targeting the Wnt pathway in human cancers: Therapeutic targeting with a focus on OMP-54F28

McDermott

Jimeno

2015

Pharmacology & Therapeutics

210

167

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The Wnt signaling pathways are a group of signal transduction pathways that play an important role in cell fate specification, cell proliferation and cell migration. Aberrant signaling in these pathways has been implicated in the development and progression of multiple cancers by allowing increased proliferation, angiogenesis, survival and metastasis. Activation of the Wnt pathway also contributes to the tumorigenicity of cancer stem cells (CSCs). Therefore, inhibiting this pathway has been a recent focus for cancer research with multiple targetable candidates in development. OMP-54F28 is a fusion protein that combines the cysteine-rich domain of frizzled family receptor 8 (Fzd8) with the immunoglobulin Fc domain that competes with the native Fzd8 receptor for its ligands and antagonizes Wnt signaling. Preclinical models with OMP-54F28 have shown reduced tumor growth and decreased CSC frequency as a single agent and in combination with other chemotherapeutic agents. Due to these findings, a phase 1a study is nearing completion with OMP-54F28 in advanced solid tumors and 3 phase 1b studies have been opened with OMP-54F28 in combination with standard of care chemotherapy backbones in ovarian, pancreatic and hepatocellular cancers. This article will review the Wnt signaling pathway, preclinical data on OMP-54F28 and other Wnt pathway inhibitors and ongoing clinical trials.

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Section: Targeting the Wnt Pathwaymentioning

confidence: 99%

Targeting the Wnt pathway in human cancers: Therapeutic targeting with a focus on OMP-54F28

McDermott

Jimeno

2015

Pharmacology & Therapeutics

210

167

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“…Salinomycin may target chemoresistant tumor cells, inhibiting Wnt/β-catenin and Sonic Hedgehog signaling pathways (Managò et al, 2015). Furthermore, it suppresses the migration of colorectal, breast, lung and colon cancer cell lines as well the invasion of nasopharyngeal carcinoma and bladder cancer cells in vitro (Kopp et al, 2014;Wu et al, 2014;Qu et al, 2015;Klose et al, 2016). Consistently, in vivo studies proved that salinomycin may reduce metastasis formation in mammary tumor mouse model, bladder tumor rat model and intravenous mouse tumor model (Gupta et al, 2009;Kopp et al, 2014;Qu et al, 2015).…”

Section: Therapeutic Targeting Metastasismentioning

confidence: 71%

Mitochondrial Involvement in Migration, Invasion and Metastasis

Denisenko

Горбунова

Zhivotovsky

2019

Front. Cell Dev. Biol.

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Mitochondria in addition to be a main cellular power station, are involved in the regulation of many physiological processes, such as generation of reactive oxygen species, metabolite production and the maintenance of the intracellular Ca 2+ homeostasis. Almost 100 years ago Otto Warburg presented evidence for the role of mitochondria in the development of cancer. During the past 20 years mitochondrial involvement in programmed cell death regulation has been clarified. Moreover, it has been shown that mitochondria may act as a switchboard between various cell death modalities. Recently, accumulated data have pointed to the role of mitochondria in the metastatic dissemination of cancer cells. Here we summarize the modern knowledge concerning the contribution of mitochondria to the invasion and dissemination of tumor cells and the possible mechanisms behind that and attempts to target metastatic cancers involving mitochondria.

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“…Other The data were normalized using the genes GAPDH, ACTB, and RPL13A. *Statistically significant difference determined using the software parameters REST-384 (48) and with relative expression higher than 2 or lower than −2 studies also reported salinomycin-induced apoptosis in tumor cell lines (Fuchs et al 2009;Kim et al 2011;Kim et al 2012;Wang et al 2012;Al Dhaheri et al 2013;Zhou et al 2013;Lee et al 2014;Wu et al 2014).…”

Section: Discussionmentioning

confidence: 99%

Salinomycin efficiency assessment in non-tumor (HB4a) and tumor (MCF-7) human breast cells

Niwa

D’Epiro

Marques

et al. 2016

Naunyn-Schmiedeberg's Arch Pharmacol

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The search for anticancer drugs has led researchers to study salinomycin, an ionophore antibiotic that selectively destroys cancer stem cells. In this study, salinomycin was assessed in two human cell lines, a breast adenocarcinoma (MCF-7) and a non-tumor breast cell line (HB4a), to verify its selective action against tumor cells. Real-time assessment of cell proliferation showed that HB4a cells are more resistant to salinomycin than MCF-7 tumor cell line, and these data were confirmed in a cytotoxicity assay. The half maximal inhibitory concentration (IC50) values show the increased sensitivity of MCF-7 cells to salinomycin. In the comet assay, only MCF-7 cells showed the induction of DNA damage. Flow cytometric analysis showed that cell death by apoptosis/necrosis was only induced in the MCF-7 cells. The increased expression of GADD45A and CDKN1A genes was observed in all cell lines. Decreased expression of CCNA2 and CCNB1 genes occurred only in tumor cells, suggesting G2/M cell cycle arrest. Consequently, cell death was activated in tumor cells through strong inhibition of the antiapoptotic genes BCL-2, BCL-XL, and BIRC5 genes in MCF-7 cells. These data demonstrate the selectivity of salinomycin in killing human mammary tumor cells. The cell death observed only in MCF-7 tumor cells was confirmed by gene expression analysis, where there was downregulation of antiapoptotic genes. These data contribute to clarifying the mechanism of action of salinomycin as a promising antitumor drug and, for the first time, we observed the higher resistance of HB4a non-tumor breast cells to salinomycin.

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Salinomycin inhibits proliferation and induces apoptosis of human nasopharyngeal carcinoma cell in vitro and suppresses tumor growth in vivo

Cited by 25 publications

References 39 publications

Targeting the Wnt pathway in human cancers: Therapeutic targeting with a focus on OMP-54F28

Targeting the Wnt pathway in human cancers: Therapeutic targeting with a focus on OMP-54F28

Mitochondrial Involvement in Migration, Invasion and Metastasis

Salinomycin efficiency assessment in non-tumor (HB4a) and tumor (MCF-7) human breast cells

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