Salinomycin as a potent anticancer stem cell agent: State of the art and future directions

Qi, Dan; Liu, Yunyi; Li, Juan; Huang, Jason H.; Hu, Xiaoxiao; Wu, Erxi

doi:10.1002/med.21870

Cited by 41 publications

(24 citation statements)

References 227 publications

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“…Furthermore, salinomycin and the other ionophores are known to kill cancer stem cells through different mechanisms, which include the modulation of signaling pathways, the initiation of autophagy, mitochondrial dysfunction, oxidative stress, and apoptosis [ 39 ]. Thus, it is possible that one or more of these mechanisms might also be involved in the observed anti- Leishmania activity.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Antiparasitic Activities of Monovalent Ionophore Compounds for Human and Canine Leishmaniases

Calvo-Álvarez

D’Alessandro

Proverbio

et al. 2022

Animals

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The leishmaniases are vector-borne parasitic diseases affecting humans and animals, with high mortality rates in endemic countries. Infected dogs represent the main reservoir of infection. Disease control is mainly based on chemotherapy, which, at present, shows serious drawbacks both in humans and dogs. Therefore, the discovery or repurposing of new treatments is mandatory. Here, three monovalent ionophores (salinomycin, monensin, nigericin) were tested against promastigotes of Leishmania (L.) infantum, Leishmania tropica, and Leishmania braziliensis, and against amastigotes of L. infantum within human and, for the first time, canine macrophages. All three drugs were leishmanicidal against all Leishmania spp. promastigotes with IC50 values between 7.98 and 0.23 µM. Monensin and nigericin showed IC50 values < 1 µM, whereas salinomycin was the least active compound (IC50 > 4 µM). Notably, the ionophores killed L. infantum amastigotes within human THP-1 cells with IC50 values ranging from 1.67 to 1.93 µM, but they only reduced by 27–37% the parasite burden in L. infantum-infected canine macrophages, showing a host-specific efficacy. Moreover, a selective higher toxicity against canine macrophages was observed. Overall, repurposed ionophores have the potential to be further investigated as anti-Leishmania agents, but different drug options may be required to tackle human or canine leishmaniases.

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Section: Discussionmentioning

confidence: 99%

In Vitro Antiparasitic Activities of Monovalent Ionophore Compounds for Human and Canine Leishmaniases

Calvo-Álvarez

D’Alessandro

Proverbio

et al. 2022

Animals

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“…Among the various anti-CSC natural compounds screened, salinomycin isolated from Streptomyces albicans has proven to be a perfect candidate for killing CSCs. 103 Basu et al developed lipid nanocapsules (LNCs) coloaded with PTX and salinomycin, which showed superior drug loading capacity and storage stability. Its lipid properties facilitate efficient cellular uptake, delivering drugs to breast cancer cells and CSCs simultaneously.…”

Section: Npns Targeting Cscsmentioning

confidence: 99%

Natural Products-Based Nanoformulations: A New Approach Targeting CSCs to Cancer Therapy

Liao¹,

Li²,

Wang

et al. 2022

IJN

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Cancer stem cells (CSCs) lead to the occurrence and progression of cancer due to their strong tumorigenic, self-renewal, and multidirectional differentiation abilities. Existing cancer treatment methods cannot effectively kill or inhibit CSCs but instead enrich them and produce stronger proliferation, invasion, and metastasis capabilities, resulting in cancer recurrence and treatment resistance, which has become a difficult problem in clinical treatment. Therefore, targeting CSCs may be the most promising approach for comprehensive cancer therapy in the future. A variety of natural products (NP) have significant antitumor effects and have been identified to target and inhibit CSCs. However, pharmacokinetic defects and off-target effects have greatly hindered their clinical translation. NP-based nanoformulations (NPNs) have tremendous potential to overcome the disadvantages of NP against CSCs through site-specific delivery and by improving their pharmacokinetic parameters. In this review, we summarize the recent progress of NPNs targeting CSCs in cancer therapy, looking forward to transforming preclinical research results into clinical applications and bringing new prospects for cancer treatment.

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“…However, these limitations can get overruled by investigating targeted delivery approaches or synthesizing their more specific and less toxic analogs. Recent research has reported the successful utilization of nanomicelles, nanoparticles, nanotubes, and cell surface markers (CD133 and CD44) conjugated multilamellar liposomes for targeted and efficient delivery of salinomycin [ 83 , 84 , 85 , 86 , 87 ].…”

Section: Natural Polyether Ionophores Antibiotics As Potent Anticance...mentioning

confidence: 99%

Evidence of Metallic and Polyether Ionophores as Potent Therapeutic Drug Candidate in Cancer Management

et al. 2022

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Cancer remains one of the most crucial human malignancies with a higher mortality rate globally, and is predicted to escalate soon. Dysregulated ion homeostasis in cancerous cells prompted the researchers to investigate further ion homeostasis impeding agents as potent anticancerous agents. Reutilization of FDA-approved non-cancerous drugs has emerged as a practical approach to developing potent, cost-effective drugs for cancer treatment. Across the globe, most nations are incapable of fulfilling the medical demands of cancer patients due to costlier cancerous drugs. Therefore, we have inclined our review towards emphasizing recent advancements in cancer therapies involving ionophores utilization in exploring potent anticancer drugs. Numerous research reports have established the significant anticancerous potential of ionophores in several pre-clinical reports via modulating aberrant cell signaling pathways and enhancing antitumor immunity in immune cells. This review has mainly summarized the most significant ion homeostasis impeding agents, including copper, zinc, calcium, and polyether, that presented remarkable potential in cancer therapeutics via enhanced antitumor immunity and apoptosis induction. Altogether, this study could provide a robust future perspective for developing cost-effective anticancerous drugs rapidly and cost-effectively, thereby combating the limitations of currently available drugs used in cancer treatment.

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Salinomycin as a potent anticancer stem cell agent: State of the art and future directions

Cited by 41 publications

References 227 publications

In Vitro Antiparasitic Activities of Monovalent Ionophore Compounds for Human and Canine Leishmaniases

In Vitro Antiparasitic Activities of Monovalent Ionophore Compounds for Human and Canine Leishmaniases

Natural Products-Based Nanoformulations: A New Approach Targeting CSCs to Cancer Therapy

Evidence of Metallic and Polyether Ionophores as Potent Therapeutic Drug Candidate in Cancer Management

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