The natural flavones, acacetin and apigenin, induce Cdk-Cyclin mediated G2/M phase arrest and trigger ROS-mediated apoptosis in glioblastoma cells

Anil Khushalrao Shendge, Dipankar Chaudhuri, Nripendranath Mandal

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Brain and CNS-related cancers are rare; however, 0.3 million incidences and 0.24 million deaths in 2018 demonstrates the unrelenting associated dangers. Glioblastoma is a brain cancer of star-shaped glial cells. It is almost universally fatal within 2 years of diagnosis despite maximal medical therapies. This study aims to evaluate the in-depth anticancer activity of acacetin and apigenin on glioblastoma cells (U87). In the present report, we have isolated two flavonoids, acacetin and apigenin; and studied the in-depth anticancer activity on U87 cells. Selective cytotoxicity of acacetin and apigenin was observed towards the U87 cells (IC50: 43.73 ± 1.19 and 48.18 ± 1.37 μM, respectively). The flow cytometer-based result revealed the induction of G2/M phase arrest along with the increase in sub G1 population upon compound treatment. Annexin-V-FLUOS and DAPI staining also confirmed the apoptosis-inducing effects of compounds. Flow cytometer and confocal microscopy-based DCFH-DA staining showed ROS-inducing effect of the compounds. The up-regulation of p21 and down-regulation of Cyclin-A1, Cyclin-B1, and Cdk-1 revealed the G2/M phase arrest mechanism of acacetin and apigenin. Furthermore, western blotting result confirmed the activation of intrinsic pathway of apoptosis upon acacetin treatment and activation of both extrinsic and intrinsic pathways of apoptosis upon apigenin treatment through the regulation of Bax, t-Bid, caspase 8, caspase 9, caspase 3, and PARP. The obtained result showed a significant effect (P < 0.05) of acacetin and apigenin on U87 cells. Acacetin and apigenin-induced ROS is responsible for the induction of cell cycle arrest and activation of caspase-cascade pathways in U87 cells.

Original languageEnglish
Pages (from-to)539-549
Number of pages11
JournalMolecular Biology Reports
Volume48
Issue number1
DOIs
StatePublished - 1 Jan 2021
Externally publishedYes

Keywords

  • Flavonoids
  • Medicinal plants
  • ROS-induction
  • U87 cell line
  • anticancer activity
  • caspase-cascade pathway

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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