The role of ceranib-2 and its nanoform on the decrease of telomerase levels in human non-small cell cancer
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Tarih
2024
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Springer
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
BackgroundCeranib-2, an acid ceramidase (AC) inhibitor, can inhibit cancer cell proliferation and tumor development. However, poor water solubility and low cellular bioavailability limit its efficacy in cancer treatment.Methods and resultsThis study aimed to investigate the cell death induced by ceranib-2 and its solid lipid nanoformulation (ceranib-2-SLN) produced by the hot homogenization technique and the synergistic relationship between ceramide and telomerase in vitro and in silico. Furthermore, this study proved the possible mechanism of ceranib-2-induced AC inhibition by in silico studies. The effective cytotoxic concentrations of ceranib-2, telomerase level, and changes in ceramide levels were measured by MTT colorimetric cytotoxicity assay, ELISA, and LC/MS/MS methods, respectively. TEM results showed that ceranib-2-SLN was 13-fold smaller than the size of ceranib-2. Ceranib-2 and ceranib-2-SLN had IC50 concentrations of 31.62 (+/- 2.1) and 27.69 (+/- 1.75) mu M in A549, and 48.79 (+/- 1.56) and 67.98 (+/- 2.33) in Beas-2B cells. These compounds simultaneously increased ceramide levels and decreased telomerase levels in A549 cells. Ceranib-2 increased telomerase levels while decreasing ceramide levels in Beas-2B cells. It was shown how the synergistic impact of ceranib-2-induced ceramide production and ceramide-induced telomerase level reduction on cytotoxicity in A549 cells.ConclusionsCeranib-2-SLN was discovered to be more cytotoxic on cancer cells than ceranib-2, suggesting that it could be a promising option for the development of a new anti-cancer agent.
Açıklama
Anahtar Kelimeler
Acid ceramidase inhibition, Ceramide, Cytotoxicity, in silico, Telomerase
Kaynak
Molecular Biology Reports
WoS Q Değeri
N/A
Scopus Q Değeri
Q2
Cilt
51
Sayı
1
