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

• Published in: Molecular biology reports 2024-12, Vol.51 (1), p.889, Article 889
• Main Authors: Cengiz, Mustafa, Sezer, Canan Vejselova, Gür, Bahri, Bayrakdar, Alpaslan, İzgördü, Hüseyin, Alanyalı, Filiz, Öziç, Cem, Kutlu, Hatice Mehtap
• Format: Article
• Language: English
• Subjects: A549 Cells; Animal Anatomy; Animal Biochemistry; Antineoplastic Agents - pharmacology; Antineoplastic drugs; Bioavailability; Biomedical and Life Sciences; Cancer; Cancer therapies; Cell death; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Ceramidase; Ceramide; Ceramides - metabolism; Colorimetry; Cytotoxicity; Enzyme-linked immunosorbent assay; Histology; Humans; Life Sciences; Morphology; Nanoparticles - chemistry; Original Article; Telomerase; Telomerase - antagonists & inhibitors; Telomerase - metabolism
• ISSN: 0301-4851; 1573-4978; 1573-4978
• DOI: 10.1007/s11033-024-09838-2

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 IC 50 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. Graphical Abstract