Deciphering the DNA-binding affinity, cytotoxicity and apoptosis induce as the anticancer mechanism of Bavachinin: An experimental and computational investigation

One of the most important mechanism by which bioflavonoids can exert their effects in cancer treatment, is through their interaction with bio-macromolecules such as DNA. Recent literature emphasizes the role of Bavachinin (BVC) as an emerging anticancer agent. However, there are no reports on its ability to interact with DNA. The present study investigated the DNA binding properties of BVC by many spectroscopic and computational approaches. The evidences are provided from UV–visible and CD spectral analyses illustrated that BVC interacted with ctDNA through minor groove binding mode. Based on the thermodynamic analyses, it can be inferred that the binding process was spontaneous, and the hydrophobic interaction played a major role in BVC-ctDNA binding. In silico molecular docking and dynamic simulation finally strengthened our experimental results that BVC was located in the minor groove (AT- rich) region of B-DNA structure and resulted in the slight alteration in the secondary structure of DNA during the interaction process. Additionally, BVC indicated significant cytotoxicity against MCF-7 breast cancer cells. Furthermore, quantitative analyses demonstrate that BVC treatment significantly increased the expression of pro-apoptotic genes; p53, caspase-3, -8, and -9 in MCF-7 cells. In order to further investigate the molecular targets of BVC, molecular docking studies indicated a relatively good binding affinity of BVC with pro-apoptotic proteins. In effect, BVC can be considered as a small organic compound with DNA binding property, appropriate cytotoxic activity, and potential of apoptotic inducing that can be adopted for medical science and pharmacy.