Cyproheptadine causes apoptosis and decreases inflammation by disrupting thiol/disulfide balance and enhancing the levels of SIRT1 in C6 glioblastoma cells

Kacar S., Hacioglu C., Kar F., Sahinturk V., Kanbak G.

TOXICOLOGY IN VITRO, cilt.73, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 73
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1016/j.tiv.2021.105135
  • Dergi Adı: TOXICOLOGY IN VITRO
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: Cyproheptadine, Glioblastoma cells, Thiol, disulfide balance, Inflammation, Apoptosis, Cytotoxicity, Annexin V, HISTAMINE, GROWTH, ASSAY
  • Eskişehir Osmangazi Üniversitesi Adresli: Evet

Özet

Cyproheptadine is first-generation antihistamine drug, that is, H1 receptor antagonist, with a drug being anesthetic, anti-serotonergic and anti-cholinergic and started to be used clinically in the 1960s. As firstly utilized as an anti-allergic drug, usage of cyproheptadine was expanded to other cases including serotonin syndrome, appetite increasing, migraines and insomnia. However, there are almost few studies seeking to explore the association between cyproheptadine and cancer in general. In the present study, we sought to determine the impact of cyproheptadine on C6 glioblastoma cells by morphological, biochemical and cytotoxic analyzes. We searched the effective doses of cyproheptadine for C6 glioblastoma cells and examined the cells under an inverted microscope. Next, we determined the protein levels of SIRT1, NF?B and IL-6 protein. Then, we measured and calculated the levels of thiols, disulfide bonds and related parameters. After that, we evaluated apoptotic activity by Annexin V and caspase 3 assays. As a result, we detected a dose-dependent increase in apoptosis and SIRT 1 protein levels, and a decrease in inflammatory proteins. Furthermore, we have detected a drop in thiol and disulfide content. Our study suggests that Cyproheptadine causes apoptosis and decreases inflammation by disrupting thiol/disulfide balance and enhancing the levels of SIRT1, offering the potential for being an anticancer drug. Therefore, it might be further investigated in future studies.