Salinomycin inhibits canine mammary carcinoma in vitro by targeting cancer stem cells

Du, Hongchao; Zhou, Bin; Zhang, Hong; Jin, Yipeng; Zhang, Di; Lin, Degui

doi:10.3892/ol.2017.6164

Cited by 10 publications

(6 citation statements)

References 33 publications

(49 reference statements)

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“…Several studies with HBC cell lines demonstrated that salinomycin inhibits in vitro growth by inducing apoptosis and selectively targeting CSC ( 412 – 419 ). Likewise, salinomycin was found to have a profound effect in CMC cell lines by selectively depleting canine mammary CSC and inhibiting the Wnt/β-catenin signaling pathway (preventing cell invasion and migration) ( 420 , 421 ).…”

Section: Other Adjuvant Therapiesmentioning

confidence: 99%

From Conventional to Precision Therapy in Canine Mammary Cancer: A Comprehensive Review

et al. 2021

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Canine mammary tumors (CMTs) are the most common neoplasm in intact female dogs. Canine mammary cancer (CMC) represents 50% of CMTs, and besides surgery, which is the elective treatment, additional targeted and non-targeted therapies could offer benefits in terms of survival to these patients. Also, CMC is considered a good spontaneous intermediate animal model for the research of human breast cancer (HBC), and therefore, the study of new treatments for CMC is a promising field in comparative oncology. Dogs with CMC have a comparable disease, an intact immune system, and a much shorter life span, which allows the achievement of results in a relatively short time. Besides conventional chemotherapy, innovative therapies have a large niche of opportunities. In this article, a comprehensive review of the current research in adjuvant therapies for CMC is conducted to gather available information and evaluate the perspectives. Firstly, updates are provided on the clinical–pathological approach and the use of conventional therapies, to delve later into precision therapies against therapeutic targets such as hormone receptors, tyrosine kinase receptors, p53 tumor suppressor gene, cyclooxygenases, the signaling pathways involved in epithelial–mesenchymal transition, and immunotherapy in different approaches. A comparison of the different investigations on targeted therapies in HBC is also carried out. In the last years, the increasing number of basic research studies of new promising therapeutic agents on CMC cell lines and CMC mouse xenografts is outstanding. As the main conclusion of this review, the lack of effort to bring the in vitro studies into the field of applied clinical research emerges. There is a great need for well-planned large prospective randomized clinical trials in dogs with CMC to obtain valid results for both species, humans and dogs, on the use of new therapies. Following the One Health concept, human and veterinary oncology will have to join forces to take advantage of both the economic and technological resources that are invested in HBC research, together with the innumerable advantages of dogs with CMC as a spontaneous animal model.

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Section: Other Adjuvant Therapiesmentioning

confidence: 99%

From Conventional to Precision Therapy in Canine Mammary Cancer: A Comprehensive Review

et al. 2021

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“…Drug repurposing has become an attractive approach due to the known pharmacological and pharmacokinetic properties of approved drugs [4, 5]. Ivermectin is a well-known anti-parasitic agent used to treat a variety of canine parasitic infestations.…”

Section: Introductionmentioning

confidence: 99%

Ivermectin inhibits canine mammary tumor growth by regulating cell cycle progression and WNT signaling

et al. 2019

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Background Mammary gland tumor is the most common spontaneous tumor in intact female dogs, and its poor prognosis remains a clinical challenge. Ivermectin, a well-known anti-parasitic agent, has been implicated as a potential anticancer agent in various types of human cancer. However, there are no reports evaluating the antitumor effects of ivermectin in canine mammary tumor. Here, we investigated whether ivermectin was able to inhibit canine mammary tumor development and explored the related mechanisms. Results Ivermectin inhibited the growth of canine mammary tumor cell lines in a dose- and time-dependent manner. The antitumor effects induced by ivermectin were associated with cell cycle arrest at G1 phase via down-regulation of CDK4 and cyclin D1 expression, with no significant induction of apoptosis. Furthermore, significantly reduced β-catenin nuclear translocation was observed after treatment with ivermectin, resulting in the inactivation of WNT signaling. Consistent with the results in vitro, a significant suppression of tumor growth by ivermectin was observed in canine mammary tumor xenografts. Conclusion Ivermectin, as a promising anti-cancer agent, inhibits the growth of canine mammary tumor by regulating cell cycle progression and WNT signaling. Electronic supplementary material The online version of this article (10.1186/s12917-019-2026-2) contains supplementary material, which is available to authorized users.

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“…Spheres derived from CF41.Mg cells exhibit stemness features such as chemoresistance to doxorubicin and paclitaxel, auto-renewal and high expression of CD44 + /CD24 -/low phenotype (Torres et al 2015). In this regard, the literature indicates that spheres from different canine mammary tumor cell lines exhibit common stemness characteristics as already described (Michishita et al 2011, Rybicka and Krol 2016, Du et al 2017. Therefore, CF41.Mg--spheres are a good model for studying CSC in response to several cytotoxic agents.…”

Section: Discussionmentioning

confidence: 73%

Polish Journal of Veterinary Sciences

Cruz

Reyes

Torres

2018

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The presence of cancer stem-like cells (CSC) within canine mammary tumors, may explain partly local recurrence and spreading, since their ability to resist conventional antitumor treatments as chemo and radiotherapy. It has been recently described that simvastatin -a drug that inhibits synthesis of cholesterol -attenuates the proliferation of canine mammary CSC derived from CF41.Mg canine mammary carcinoma cells, promoting their chemosensitizing and apoptosis. The canonical Wnt/β-catenin pathway is usually activated at CSC and up-regulates multidrug resistance protein 1 (MDR1), triggering chemoresistance. In the present study, we analyze the effect of simvastatin on β-catenin/MDR1 expression in spheres obtained from the CF41.Mg cell line as a model of CSC.Simvastatin increased phosphorylation of β-catenin without affecting its total expression. Moreover, MDR1 expression was decreased by simvastatin. These results suggest that simvastatin would facilitate the degradation of β-catenin, decreasing MDR1 expression and contributing to the chemosensitizing effects of the statin on canine mammary CSC.

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Salinomycin inhibits canine mammary carcinoma in vitro by targeting cancer stem cells

Cited by 10 publications

References 33 publications

From Conventional to Precision Therapy in Canine Mammary Cancer: A Comprehensive Review

From Conventional to Precision Therapy in Canine Mammary Cancer: A Comprehensive Review

Ivermectin inhibits canine mammary tumor growth by regulating cell cycle progression and WNT signaling

Polish Journal of Veterinary Sciences

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