Preclinical drug metabolism and pharmacokinetics of salinomycin, a potential candidate for targeting human cancer stem cells

Resham, Kahkashan; Patel, Prinesh N.; Thummuri, Dinesh; Guntuku, Lalita; Shah, Vanya; Bambal, Ramesh; Naidu, V.G.M.

doi:10.1016/j.cbi.2015.08.007

Cited by 25 publications

(22 citation statements)

References 21 publications

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“…Similar results were also observed previously [71]. In a recent study, SLM was reported to be highly protein bound with limited availability in systemic circulation [72]. But protein binding efficiency was decreased as SLM was encapsulated in nanoparticles.…”

Section: Specificity Of Nanoparticles To Cd44 Binding On Mda-mb-231 Csupporting

confidence: 88%

CD44 targeted chemotherapy for co-eradication of breast cancer stem cells and cancer cells using polymeric nanoparticles of salinomycin and paclitaxel

Muntimadugu

Kumar

Saladi

et al. 2016

Colloids and Surfaces B: Biointerfaces

157

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Section: Specificity Of Nanoparticles To Cd44 Binding On Mda-mb-231 Csupporting

confidence: 88%

CD44 targeted chemotherapy for co-eradication of breast cancer stem cells and cancer cells using polymeric nanoparticles of salinomycin and paclitaxel

Muntimadugu

Kumar

Saladi

et al. 2016

Colloids and Surfaces B: Biointerfaces

157

View full text Add to dashboard Cite

“…Salinomycin is a promising drug against various CSCs in various types of cancer [9] . Not only did salinomycin show potent anti-CSC activity in several preclinical experimental studies, including in a variety of cancer cell lines and in mice bearing human cancer xenografts [9] , it has been tested in a few clinical pilots, which revealed that salinomycin could eliminate CSCs and induce regression of therapy-resistant cancers [11] . However, whether salinomycin could target melanoma CSCs has been never investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Salinomycin, an antibacterial therapeutic drug, has emerged as an effective drug toward various CSCs in a variety of cancers [9] . It was first discovered by Gupta et al who used a highthroughput screening approach that identified salinomycin as a promising drug against breast CSCs [10] .…”

Section: Introductionmentioning

confidence: 99%

Salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers selectively suppress human CD20+ melanoma stem cells

Zeng

et al. 2017

Acta Pharmacol Sin

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Melanoma is the deadliest type of skin cancer. CD20+ melanoma stem cells (CSCs) are pivotal for metastasis and initiation of melanoma. Therefore, selective elimination of CD20+ melanoma CSCs represents an effective treatment to eradicate melanoma. Salinomycin has emerged as an effective drug toward various CSCs. Due to its poor solubility, its therapeutic efficacy against melanoma CSCs has never been evaluated. In order to target CD20+ melanoma CSCs, we designed salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers (CD20-SA-NPs). Using a single-step nanoprecipitation method, salinomycin-loaded lipid-polymer nanoparticles (SA-NPs) were prepared, then CD20-SA-NPs were obtained through conjugation of thiolated anti-CD20 aptamers to SA-NPs via a maleimide-thiol reaction. CD20-SA-NPs displayed a small size of 96.3 nm, encapsulation efficiency higher than 60% and sustained drug release ability. The uptake of CD20-SA-NPs by CD20+ melanoma CSCs was significantly higher than that of SA-NPs and salinomycin, leading to greatly enhanced cytotoxic effects in vitro, thus the IC values of CD20-SA-NPs were reduced to 5.7 and 2.6 μg/mL in A375 CD+20 cells and WM266-4 CD+ cells, respectively. CD20-SA-NPs showed a selective cytotoxicity toward CD20+ melanoma CSCs, as evidenced by the best therapeutic efficacy in suppressing the formation of tumor spheres and the proportion of CD20+ cells in melanoma cell lines. In mice bearing melanoma xenografts, administration of CD20-SA-NPs (salinomycin 5 mg·kg·d, iv, for 60 d) showed a superior efficacy in inhibition of melanoma growth compared with SA-NPs and salinomycin. In conclusion, CD20 is a superior target for delivering drugs to melanoma CSCs. CD20-SA-NPs display effective delivery of salinomycin to CD20+ melanoma CSCs and represent a promising treatment for melanoma.

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“…It was reported in inhibiting colon cancer growth (7,15 (9). Salinomycin has been evaluated by several studies in various types of cancer stem cells (16)(17)(18)(19)(20). Salinomycin downregulated the expression of IGFBP-4 and certain other genes compared with Paclitaxel treatment.…”

Section: Discussionmentioning

confidence: 99%

IGFBP‑4 expression is adversely associated with lung cancer prognosis

et al. 2017

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Abstract. Insulin-like growth factor binding protein-4 (IGFBP-4) was reported to be associated with prognosis in several types of cancer; however, to the best of our knowledge, whether it is correlated with lung cancer has yet to be reported. In the present study, 102 pairs of lung cancer tissues and surrounding non-cancerous tissues (SNCTs) were collected. The IGFBP-4 levels in tissues were detected with immunohistochemistry. The relevance of IGFBP-4 to the survival of patients was assessed. The IGFBP-4 gene was knocked down, and its function in the proliferation of lung cancer cells was measured. The percentage of lung cancer tissues with higher IGFBP-4 expression than SNCTs (51.9%) was increased compared with the percentage with similar (11.76%) or lower (36.27%) IGFBP-4 expression. Patients with higher IGFBP-1 expression exhibited a shorter median survival time. IGFBP-1 was associated with metastasis, lung cancer stages and malignancy, but not with age, sex or tumor size. Lung cancer cells with stably knocked down IGFBP-4 showed an inhibitory proliferation rate. The present study identified that IGFBP-4 was adversely associated with the prognosis of lung cancer patients. IGFBP-4 knockdown prohibited lung cancer cell growth. The present study provides a potential marker for lung cancer diagnosis and a possible target for lung cancer therapy.

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Preclinical drug metabolism and pharmacokinetics of salinomycin, a potential candidate for targeting human cancer stem cells

Cited by 25 publications

References 21 publications

CD44 targeted chemotherapy for co-eradication of breast cancer stem cells and cancer cells using polymeric nanoparticles of salinomycin and paclitaxel

CD44 targeted chemotherapy for co-eradication of breast cancer stem cells and cancer cells using polymeric nanoparticles of salinomycin and paclitaxel

Salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers selectively suppress human CD20+ melanoma stem cells

IGFBP‑4 expression is adversely associated with lung cancer prognosis

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