Cell experiment:

NSCLC, NCI-H1299, NCI-H460, WI-26 VA4 and MRC-5 cell lines are exposed to a single dose of γ-rays. Cells are then treated with rhamnetin and cirsiliol (5, 10, 15, 20, 25 μM) dissolved in DMSO for 4 h[2].

Animal experiment:

Mice[1]BALB/c athymic nude mice are injected with 2×106 NCI-H1299 cells. When the tumor has acquired a minimal volume of 200 mm3, DMSO or Cirsiliol (200 μg/kg body weight) is administered intraperitoneally every day for 25 days. The animals are also irradiated with 10 Gy once a week for 3 weeks. On day 25, the tumors are excised and subjected to further analyses[1].

Cirsiliol is a potent and selective 5-lipoxygenase inhibitor and a competitive low affinity benzodiazepine receptor ligand.

In concentrations from 0.01 to 300 μM, cirsiliol causes concentration-dependent relaxation of rat isolated ileum. Cirsiliol may inhibit Ca2+ influx but stimulates Ca2+ release from intracellular stores[1]. Treatment with rhamnetin or cirsiliol reduces the proliferation of NSCLC cells through the suppression of radiation-induced Notch-1 expression[2].

In xenograft mouse model, tumor volume is significantly reduced by combinational treatment with irradiation and rhamnetin or cirsiliol compared with irradiation alone[2].

[1]. Mustafa EH, et al. Effects of cirsiliol, a flavone isolated from Achillea fragrantissima, on rat isolated ileum. Gen Pharmacol. 1992 May;23(3):555-60. [2]. Kang J, et al. Rhamnetin and cirsiliol induce radiosensitization and inhibition of epithelial-mesenchymal transition (EMT) by miR-34a-mediated suppression of Notch-1 expression in non-small cell lung cancer cell lines. J Biol Chem. 2013 Sep 20;288(38):27343-57.