Single and double modified salinomycin analogs target stem-like cells in 2D and 3D breast cancer models

Urbaniak, Alicja; Reed, Megan R.; Fil, Daniel; Moorjani, Anika; Heflin, Sarah; Antoszczak, Michał; Šulik, Michal; Huczyński, Adam; Kupsik, Michalina; Eoff, Robert L.; MacNicol, Melanie C.; Chambers, Timothy C.; MacNicol, Angus M.

doi:10.1016/j.biopha.2021.111815

Cited by 8 publications

(11 citation statements)

References 94 publications

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“…Cancer organoids were generated as shown in Fig. 3A according to our previously published protocol [ 32 ]. Briefly, droplets of a complete NeuroCult and Matrigel in 1:4 ratio, containing 8 × 10^3 U-118 MG cells/droplet were generated by pipetting 20 μl of the cold mixture (stored on ice) onto a base mold of Parafilm.…”

Section: Methodsmentioning

confidence: 99%

Anti-glioblastoma activity of monensin and its analogs in an organoid model of cancer

Urbaniak

Reed

Heflin

et al. 2022

Biomedicine & Pharmacotherapy

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Section: Methodsmentioning

confidence: 99%

Anti-glioblastoma activity of monensin and its analogs in an organoid model of cancer

Urbaniak

Reed

Heflin

et al. 2022

Biomedicine & Pharmacotherapy

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“…For instance, smart liposomebased systems co-delivering doxorubicin and salinomycin were found effective in reducing stemness in liver CSCs [309] whereas a combination of salinomycin and docetaxel loaded onto PNPs proved a promising strategy when targeting gastric CSCs [311]. Besides co-delivery systems, preclinical studies also show salinomycin derivates as capable of targeting CSCs successfully on their own, although predominantly within breast cancers models [321][322][323].…”

Section: Nanocarrier-based Cancer Therapeuticsmentioning

confidence: 99%

Cancer Stem Cells and the Tumor Microenvironment: Targeting the Critical Crosstalk through Nanocarrier Systems

Nayak

Warrier

Kumar

2022

Stem Cell Rev and Rep

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The physiological state of the tumor microenvironment (TME) plays a central role in cancer development due to multiple universal features that transcend heterogeneity and niche specifications, like promoting cancer progression and metastasis. As a result of their preponderant involvement in tumor growth and maintenance through several microsystemic alterations, including hypoxia, oxidative stress, and acidosis, TMEs make for ideal targets in both diagnostic and therapeutic ventures. Correspondingly, methodologies to target TMEs have been investigated this past decade as stratagems of significant potential in the genre of focused cancer treatment. Within targeted oncotherapy, nanomedical derivates—nanocarriers (NCs) especially—have emerged to present notable prospects in enhancing targeting specificity. Yet, one major issue in the application of NCs in microenvironmental directed therapy is that TMEs are too broad a spectrum of targeting possibilities for these carriers to be effectively employed. However, cancer stem cells (CSCs) might portend a solution to the above conundrum: aside from being quite heavily invested in tumorigenesis and therapeutic resistance, CSCs also show self-renewal and fluid clonogenic properties that often define specific TME niches. Further scrutiny of the relationship between CSCs and TMEs also points towards mechanisms that underly tumoral characteristics of metastasis, malignancy, and even resistance. This review summarizes recent advances in NC-enabled targeting of CSCs for more holistic strikes against TMEs and discusses both the current challenges that hinder the clinical application of these strategies as well as the avenues that can further CSC-targeting initiatives. Graphical abstract Central role of CSCs in regulation of cellular components within the TME

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“…This includes Wnt/β-catenin, PI3K/Akt/mTOR, K-Ras, as well as Hedgehog signaling. 11 − 15 With respect to the very promising biological activity of Sal , a number of its semisynthetic analog structures have been developed, 16 − 30 some of which exhibit relevant activity against cancer cells with stemlike characteristics. 25 , 30 − 34 …”

Section: Introductionmentioning

confidence: 99%

“…Mechanistically, many pathways and molecular complexes that confer resistance and survival of CSCs have been identified to be significantly modulated after Sal treatment. This includes Wnt/β-catenin, PI3K/Akt/mTOR, K-Ras, as well as Hedgehog signaling. − With respect to the very promising biological activity of Sal , a number of its semisynthetic analog structures have been developed, − some of which exhibit relevant activity against cancer cells with stemlike characteristics. ,− …”

Section: Introductionmentioning

confidence: 99%

Rapid Access to Ironomycin Derivatives by Click Chemistry

et al. 2022

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Salinomycin, a natural carboxylic polyether ionophore, shows a very interesting spectrum of biological activities, including selective toxicity toward cancer stem cells (CSCs). Recently, we have developed a C20-propargylamine derivative of salinomycin (ironomycin) that exhibits more potent activity in vivo and greater selectivity against breast CSCs compared to the parent natural product. Since ironomycin contains a terminal alkyne motif, it stands out as being an ideal candidate for further functionalization. Using copper-catalyzed azide–alkyne cycloaddition (CuAAC), we synthesized a series of 1,2,3-triazole analogs of ironomycin in good overall yields. The in vitro screening of these derivatives against a well-established model of breast CSCs (HMLER CD24 low /CD44 high ) and its corresponding epithelial counterpart (HMLER CD24 high /CD44 low ) revealed four new products characterized by higher potency and improved selectivity toward CSCs compared to the reference compound ironomycin. The present study highlights the therapeutic potential of a new class of semisynthetic salinomycin derivatives for targeting selectively the CSC niche and highlights ironomycin as a promising starting material for the development of new anticancer drug candidates.

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Single and double modified salinomycin analogs target stem-like cells in 2D and 3D breast cancer models

Cited by 8 publications

References 94 publications

Anti-glioblastoma activity of monensin and its analogs in an organoid model of cancer

Anti-glioblastoma activity of monensin and its analogs in an organoid model of cancer

Cancer Stem Cells and the Tumor Microenvironment: Targeting the Critical Crosstalk through Nanocarrier Systems

Rapid Access to Ironomycin Derivatives by Click Chemistry

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