Effect of HA14‐1 on Apoptosis‐Regulating Proteins in HeLa Cells. (26th December 2013)

• Record Type: Journal Article
• Authors: Rehman, Kanwal; Tariq, Muhammad; Akash, Muhammad S. H.; Gillani, Zeeshan; Qazi, Mehmood H.
• Is Part Of: Chemical biology & drug design. Volume 83:Number 3(2014:Mar.)
• Page Start: 317
• Page End: 323
• Publication Date: 2013-12-26
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12245
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" id="cbdd12245-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Overexpression of Bcl‐2 has been recognized in various malignancies. Recently, HA14‐1, a Bcl‐2 antagonist, has been identified for its anti‐apoptotic effect. However, mode of action of HA14‐1 still remains to be elucidated. In this study, we examined HA14‐1 binding efficiency with receptor proteins through molecular docking. Cell viability using HeLa cells was evaluated through MTT assay after exposure to different concentration of HA14‐1. Moreover, after HA14‐1 exposure, expressions of tumor suppressor protein (p53), BH3‐only protein (Puma) and apoptosis‐associated proteins were analyzed by Western blotting. From the results, it was found that HA14‐1 occupied all three domains; BH1, BH2, and BH3 within the hydrophobic pocket of Bcl‐2. However, HA14‐1 occupied only BH1 and BH3 of Bcl‐xl, conversely, no such stable bond was observed for Bax and Bak. ARG107 and TYR101 were the amino acids involved in the binding of HA14‐1 to Bcl‐2 and Bcl‐xl, respectively. Additionally, decrease in Bcl‐2 and Bcl‐xl expression along with increase in p53 and Puma expression after exposure to HA14‐1 was observed. The results suggested p53 pathway to be the probable mechanism of action for the induction of apoptosis in HeLa cell by downregulating the effect of anti‐apoptotic proteins suggesting that HA14‐1 may provide therapeutic potential for the treatment of human cervical cancer.</p> </abstract>