The role of ceranib-2 and its nanoform on the decrease of telomerase levels in human non-small cell cancer.

Background: Ceranib-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 results: This 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) µM 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. Conclusions: Ceranib-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. [ABSTRACT FROM AUTHOR]