Salinomycin inhibits metastatic colorectal cancer growth and interferes with Wnt/β-catenin signaling in CD133+ human colorectal cancer cells

Klose, Johannes; Eissele, Jana; Volz, Christian; Schmitt, Steffen; Ritter, Alina S.; Ying, Shao‐Yao; Schmidt, Thomas; Heger, Ulrike; Schneider, Martin; Ulrich, Alexis

doi:10.1186/s12885-016-2879-8

Cited by 42 publications

(28 citation statements)

References 41 publications

(59 reference statements)

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“…Of note is that SAL acted synergistically with 5FU towards drug-resistant A2780 OvCa cell line. A similar effect was presented in studies concerning colorectal and hepatocellular carcinoma, which indicated the neutral or synergistic effect of the combination of SAL and 5FU [48,49]. In case of GEM, which is mostly used as a secondary line of chemotherapy after the development of resistant disease in OvCa, we did not observe the synergistic effect of combined SAL and GEM in both OvCa cell lines, as was found over their action in pancreatic carcinoma cell lines [50,51].…”

Section: Discussionsupporting

confidence: 87%

Overcoming Resistance to Platinum-Based Drugs in Ovarian Cancer by Salinomycin and Its Derivatives—An In Vitro Study

et al. 2020

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Polyether ionophore salinomycin (SAL) and its semi-synthetic derivatives are recognized as very promising anticancer drug candidates due to their activity against various types of cancer cells, including multidrug-resistant populations. Ovarian cancer is the deadliest among gynecologic malignancies, which is connected with the development of chemoresistant forms of the disease in over 70% of patients after initial treatment regimen. Thus, we decided to examine the anticancer properties of SAL and selected SAL derivatives against a series of drug-sensitive (A2780, SK-OV-3) and derived drug-resistant (A2780 CDDP, SK-OV-3 CDDP) ovarian cancer cell lines. Although SAL analogs showed less promising IC50 values than SAL, they were identified as the antitumor agents that significantly overcome the resistance to platinum-based drugs in ovarian cancer, more potent than unmodified SAL and commonly used anticancer drugs—5-fluorouracil, gemcitabine, and cisplatin. Moreover, when compared with SAL used alone, our experiments proved for the first time increased selectivity of SAL-based dual therapy with 5-fluorouracil or gemcitabine, especially towards A2780 cell line. Looking closer at the results, SAL acted synergistically with 5-fluorouracil towards the drug-resistant A2780 cell line. Our results suggest that combinations of SAL with other antineoplastics may become a new therapeutic option for patients with ovarian cancer.

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Section: Discussionsupporting

confidence: 87%

Overcoming Resistance to Platinum-Based Drugs in Ovarian Cancer by Salinomycin and Its Derivatives—An In Vitro Study

et al. 2020

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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: 70%

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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“…The lower compartment of the chamber was filled with culture medium containing 20% fetal calf serum. Cells were cultured in the absence or presence of Sal for 48 h. Afterward, the medium was changed and the cells were incubated for another 48 h. Membranes were stained with crystal violet solution, and the migrated cells on the lower side of the membrane were isolated from the membrane and quantified by measurement of the absorbance at 540 nm according to the manufacturer’s instructions and as described in [ 11 ].…”

Section: Methodsmentioning

confidence: 99%

Salinomycin inhibits cholangiocarcinoma growth by inhibition of autophagic flux

et al. 2017

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IntroductionCholangiocarcinoma is characterized by aggressive tumor growth, high recurrence rates, and resistance against common chemotherapeutical regimes. The polyether-antibiotic Salinomycin is a promising drug in cancer therapy because of its ability to overcome apoptosis resistance of cancer cells and its selectivity against cancer stem cells. Here, we investigated the effectiveness of Salinomycin against cholangiocarcinoma in vivo, and analyzed interference of Salinomycin with autophagic flux in human cholangiocarcinoma cells.ResultsSalinomycin reduces tumor cell viability, proliferation, migration, invasion, and induced apoptosis in vitro. Subcutaneous and intrahepatic cholangiocarcinoma growth in vivo was inhibited upon Salinomycin treatment. Analysis of autophagy reveals inhibition of autophagic activity. This was accompanied by accumulation of mitochondrial mass and increased generation of reactive oxygen species.ConclusionsThis study demonstrates the effectiveness of Salinomycin against cholangiocarcinoma in vivo. Inhibition of autophagic flux represents an underlying molecular mechanism of Salinomycin against cholangiocarcinoma.MethodsThe two murine cholangiocarcinoma cell lines p246 and p254 were used to analyze tumor cell proliferation, viability, migration, invasion, and apoptosis in vitro. For in vivo studies, murine cholangiocarcinoma cells were injected into syngeneic C57-BL/6-mice to initiate subcutaneous cholangiocarcinoma growth. Intrahepatic tumor growth was induced by electroporation of oncogenic transposon-plasmids into the left liver lobe. For mechanistic studies in human cells, TFK-1 and EGI-1 were used, and activation of autophagy was analyzed after exposure to Salinomycin.

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Salinomycin inhibits metastatic colorectal cancer growth and interferes with Wnt/β-catenin signaling in CD133+ human colorectal cancer cells

Cited by 42 publications

References 41 publications

Overcoming Resistance to Platinum-Based Drugs in Ovarian Cancer by Salinomycin and Its Derivatives—An In Vitro Study

Overcoming Resistance to Platinum-Based Drugs in Ovarian Cancer by Salinomycin and Its Derivatives—An In Vitro Study

Mitochondrial Involvement in Migration, Invasion and Metastasis

Salinomycin inhibits cholangiocarcinoma growth by inhibition of autophagic flux

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