Hesperidin as a potent telomerase inhibitor: Studies on its anticancer and anti-telomerase effects

Lung cancer, prevalent in both genders, is associated with elevated telomerase activity (TA). Some plant-derived molecules such as boldine, resveratrol, pterostilbene and quercetin act as telomerase blockers, reducing TA in different types of malignant cells. To test more such natural inhibitors, we investigated here whether hesperidin (HSP), a naturally occurring citrus fruit ingredient, inhibits TA and affects A549 cell growth and apoptosis. We analysed cytotoxicity, cell viability, and determined the apoptotic impact of various concentrations of HSP and curcumin (CUR) in A549 cells. Morphological features were observed by phase-contrast microscopy and a telomeric repeat amplification protocol (TRAP) assay performed to quantify TA. Cytotoxic studies of HSP and CUR on erythrocytes showed no hemolysis of cells at the concentrations tested (up to 80 mu mol/ml). HSP significantly reduced TA and cell viability, in addition to an associated increase in apoptotic events in a dosedependent manner. In addition, molecular docking experiments were conducted using telomerase crystal structure. The docking results of HSP showed a strong interaction with the active site of telomerase which was an even stronger telomerase inhibitor than the control inhibitor, CUR and possessed hydrophobic, hydrogen and van der Waals interactions. These observations advocate telomerase as an intriguing potential target for lung cancer while future studies should address the exact dose and duration of HSP use in cancer therapies in vivo.