Cirsilineol inhibits proliferation of lung squamous cell carcinoma by inducing ROS mediated apoptosis

Area of Science:

• Biochemistry
• Pharmacology
• Cell Biology

Background:

• Flavones, a class of natural compounds, require further investigation for their anti-proliferative properties.
• Cirsilineol, a specific flavone, has not been extensively studied for its potential in cancer treatment.

Purpose of the Study:

• To investigate the anti-proliferative potential of cirsilineol against NCIH-520 cancer cells.
• To elucidate the mechanisms underlying cirsilineol's anti-proliferative effects, including apoptosis induction and enzyme inhibition.

Main Methods:

• Cell proliferation assays were performed on NCIH-520 and other cell lines treated with cirsilineol.
• Flow cytometry (Annexin-V-FITC assay) was used to assess apoptosis and necrosis.
• Enzyme activity assays were conducted for ornithine decarboxylase (ODC), cathepsin D (CATD), dihydrofolate reductase (DHFR), hyaluronidase (HYAL), lipoxygenase-5 (LOX-5), and cyclooxygenase-2 (COX-2).
• Reactive oxygen species (ROS) production was measured.

Main Results:

• Cirsilineol significantly inhibited NCIH-520 cell proliferation (81.96%) and other cell lines (up to 48.50%) at 100 μM.
• It induced apoptosis in a dose-dependent manner (2.64-fold at 10 μM, 5.12-fold at 100 μM) and increased ROS production (1.16-fold at 10 μM, 2.22-fold at 100 μM).
• Cirsilineol demonstrated good binding energy and inhibited key enzymes like ODC, CATD, DHFR, HYAL, LOX-5, and COX-2, with up to 45.14% inhibition at 100 μM.

Conclusions:

• Cirsilineol exhibits significant anti-proliferative activity against NCIH-520 cells, primarily through ROS-mediated apoptosis.
• The compound also shows inhibitory effects on several enzymes crucial for cell proliferation.
• Cirsilineol possesses favorable ADME properties, is non-toxic, and non-mutagenic, suggesting its potential as a herbal lead for cancer treatment or a basis for synthesizing new anti-cancer derivatives.