Inhibitory effect of AK-7 mediates by apoptosis, increases DNA fragmentation and caspase-3 activity in human glioblastoma multiforme cells

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Güçlü E., Ayan İ. Ç., Vural H.

Bangladesh Journal of Pharmacology, vol.17, no.2, pp.42-50, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 17 Issue: 2
  • Publication Date: 2022
  • Doi Number: 10.3329/bjp.v17i2.59809
  • Journal Name: Bangladesh Journal of Pharmacology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, Veterinary Science Database, Directory of Open Access Journals
  • Page Numbers: pp.42-50
  • Keywords: AK-7, Apoptosis, Glioblastoma multiforme, qRT-PCR, SIRT2 inhibitor, Sirtuin 2
  • Yozgat Bozok University Affiliated: No

Abstract

Sirtuins (SIRTs) which are nicotinamide adenine dinucleotide (NAD+) dependent class III histondeacetylases have a controversial role in cancer. In this study, the effect of pharmacological inhibition of AK-7, a SIRT2 inhibitor, was investigated in U87 glioblastoma multiforme cells. The cytotoxic effect of AK-7 was evaluated by XTT analysis. After AK-7 treatment, colony forming capacity of cells was determined and apoptosis was evaluated. The expression levels of apoptosis-related genes were determined by qRT-PCR. According to the results, AK-7 inhibited cell proliferation in a dose-and time-dependent manner. After AK-7 treatment, the colony forming capacity of U87 cells was suppressed. And, AK-7 increased apoptosis rate, DNA fragmentation, and caspase-3 activity. According to qRT-PCR, a significant increase was observed in expression levels of apoptosis-related genes. This study revealed that AK-7 inhibits cell proliferation and induces apoptosis in glioblastoma multiforme cells and SIRT2 inhibition can be evaluated as a therapeutic approach in glioblastoma multiforme.