Pretreatment of prostate cancer cells with salinomycin and Wnt inhibitor increases the efficacy of cabazitaxel by inducing apoptosis and decreasing cancer stem cells

Serttas, Rıza; Erdoğan, Suat

doi:10.1007/s12032-023-02062-1

Cited by 4 publications

(3 citation statements)

References 56 publications

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“…The stemness maintenance and acquisition of an invasive phenotype by the means of the epithelial-mesenchymal transition are key steps in cancer progression, including prostate cancer [26]. As is shown in Figure 3, a Western blot analysis of lysates from the UniPR1331-treated PC3 cells revealed a reduction in the PC3 stem marker CD44 and the inhibition of EMT markers' expression.…”

Section: Unipr1331 Inhibited Pc3 Epithelial-mesenchymal Transition (E...mentioning

confidence: 91%

A Pharmacological Investigation of Eph-Ephrin Antagonism in Prostate Cancer: UniPR1331 Efficacy Evidence

Festuccia,

Corrado,

Rossetti

et al. 2023

Pharmaceuticals

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The Eph kinases are the largest receptor tyrosine kinases (RTKs) family in humans. PC3 human prostate adenocarcinoma cells are a well-established model for studying Eph–ephrin pharmacology as they naturally express a high level of EphA2, a promising target for new cancer therapies. A pharmacological approach with agonists did not show significant efficacy on tumor growth in prostate orthotopic murine models, but reduced distal metastasis formation. In order to improve the comprehension of the pharmacological targeting of Eph receptors in prostate cancer, in the present work, we investigated the efficacy of Eph antagonism both in vitro and in vivo, using UniPR1331, a small orally bioavailable Eph–ephrin interaction inhibitor. UniPR1331 was able to inhibit PC3 cells’ growth in vitro in a dose-dependent manner, affecting the cell cycle and inducing apoptosis. Moreover, UniPR1331 promoted the PC3 epithelial phenotype, downregulating epithelial mesenchymal transition (EMT) markers. As a consequence, UniPR1331 reduced in vitro PC3 migration, invasion, and vasculomimicry capabilities. The antitumor activity of UniPR1331 was confirmed in vivo when administered alone or in combination with cytotoxic drugs in PC3-xenograft mice. Our results demonstrated that Eph antagonism is a promising strategy for inhibiting prostate cancer growth, especially in combination with cytotoxic drugs.

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Section: Unipr1331 Inhibited Pc3 Epithelial-mesenchymal Transition (E...mentioning

confidence: 91%

A Pharmacological Investigation of Eph-Ephrin Antagonism in Prostate Cancer: UniPR1331 Efficacy Evidence

Festuccia,

Corrado,

Rossetti

et al. 2023

Pharmaceuticals

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show abstract

“…Wnt-signaling in CSC can also be targeted by small antagonist molecules because of its important role in CSC renewal [148]. More recently, cabazitaxel chemotherapy of PC cells was proven to be more effective when salinomycin and a Wnt inhibitor were used as pretreatment; specifically, this regimen led to reduced cell migration and PCSC content [149].…”

Section: Targeting Pcscs For Therapymentioning

confidence: 99%

Prostate Cancer Stem Cells: Biology and Treatment Implications

Koukourakis,

Platoni,

Kouloulias

et al. 2023

IJMS

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Stem cells differentiate into mature organ/tissue-specific cells at a steady pace under normal conditions, but their growth can be accelerated during the process of tissue healing or in the context of certain diseases. It is postulated that the proliferation and growth of carcinomas are sustained by the presence of a vital cellular compartment resembling stem cells residing in normal tissues: ‘stem-like cancer cells’ or cancer stem cells (CSCs). Mutations in prostate stem cells can lead to the formation of prostate cancer. Prostate CSCs (PCSCs) have been identified and partially characterized. These express surface markers include CD44, CD133, integrin α2β1, and pluripotency factors like OCT4, NANOG, and SOX2. Several signaling pathways are also over-activated, including Notch, PTEN/Akt/PI3K, RAS-RAF-MEK-ERK and HH. Moreover, PCSCs appear to induce resistance to radiotherapy and chemotherapy, while their presence has been linked to aggressive cancer behavior and higher relapse rates. The development of treatment policies to target PCSCs in tumors is appealing as radiotherapy and chemotherapy, through cancer cell killing, trigger tumor repopulation via activated stem cells. Thus, blocking this reactive stem cell mobilization may facilitate a positive outcome through cytotoxic treatment.

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“…Tumors harbor various cell populations, including cancer stem cells (CSCs) with tumor-initiating abilities [ 5 ]. CSCs, often < 1% of tumor tissue, resist standard therapies and develop multidrug resistance [ 6 ]. They express pluripotent factors like Nanog, Oct, and Sox, and generate three-dimensional cultures [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Potent Suppression of Prostate Cancer Cell Growth and Eradication of Cancer Stem Cells by CD44-targeted Nanoliposome-quercetin Nanoparticles

Turkekul,

Erdogan

2023

J Cancer Prev

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The bioavailability of quercetin, a natural compound, is hindered by low solubility, limited absorption, and restricted systemic availability. Therefore, encapsulating it in biocompatible nanoparticles presents a promising solution. This study aimed to target prostate cancer stem cells (CSCs) overexpressing CD44+ receptors as well as cancer cells, employing quercetin-loaded hyaluronic acid-modified nanoliposomes (LP-Quer-HA). Synthesized via a green ethanol injection method, these nanoliposomes had an average diameter of 134 nm and an impressive loading efficiency of 96.9%. Human prostate cancer cells were treated with either 10 μM of free quercetin or the same concentration delivered by LP-Quer-HA for 72 hours. Free quercetin reduced androgen-resistant PC3 cell viability by 16%, while LP-Quer-HA significantly increased cell death to 60%. It induced apoptosis, upregulating cytochrome c , Bax, caspases 3 and 8, and downregulating survivin and Bcl-2 expression. Compared to free quercetin, LP-Quer-HA upregulated E-cadherin expression while inhibiting cell migration and reducing the expression of fibronectin, N-cadherin, and MMP9. Treatment of PC3 cell tumor spheroids with LP-Quer-HA decreased the number of CD44 cells and expression of CD44, Oct3/4 and Wnt. Moreover, LP-Quer-HA inhibited p-ERK expression while increasing p38/MAPK and NF-κB protein expression. In androgen-sensitive LNCaP cells, LP-Quer-HA efficacy was notable, reducing cell viability from 10% to 52% compared to free quercetin. Utilizing HA-modified nanoliposomes as a quercetin delivery system enhanced its potency at lower concentrations, reducing the CD44+ cell population and effectively impeding prostate cancer cell proliferation and migration. These findings underscore the potential of quercetin-loaded cationic nanoliposomes as a robust therapeutic approach.

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Pretreatment of prostate cancer cells with salinomycin and Wnt inhibitor increases the efficacy of cabazitaxel by inducing apoptosis and decreasing cancer stem cells

Cited by 4 publications

References 56 publications

A Pharmacological Investigation of Eph-Ephrin Antagonism in Prostate Cancer: UniPR1331 Efficacy Evidence

A Pharmacological Investigation of Eph-Ephrin Antagonism in Prostate Cancer: UniPR1331 Efficacy Evidence

Prostate Cancer Stem Cells: Biology and Treatment Implications

Potent Suppression of Prostate Cancer Cell Growth and Eradication of Cancer Stem Cells by CD44-targeted Nanoliposome-quercetin Nanoparticles

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