Cancers
Chk1/2 Inhibition by AZD7762 Enhances Andrographolide-Induced DNA Damage, Impairs DNA Repair, and Promotes Apoptosis in Head and Neck Squamous Cell Carcinoma CAL-33 Cells
By Sakshi Singh, Anitha Kartha, Aishwarya Jaiswal and 2 others.
Abstract
Background
Andrographolide (AG), a diterpenoid lactone and a major constituent of Andrographis paniculata, has shown promising antiproliferative effect on diverse cancer cell lines, including head and neck cancer. However, a significant anti-proliferative effect is observed only at high micromolar concentrations. Further, AG has been shown to have poor oral bioavailability. Therefore, it is essential to consider mechanism-based combinations that could synergistically enhance the therapeutic potential of this compound so that efficacy can be achieved in concentrations that are systemically achievable.
Objective
The present study is aimed to evaluate the anticancer effects and associated molecular alterations of an AG and Chk1/2 inhibitor combination in head and neck squamous cell carcinoma (CAL-33) cells since the earlier studies have suggested ATM/ATR/Chk1/2-mediated activation of DNA damage checkpoints.