Elucidation of S-Allylcysteine Role in Inducing Apoptosis by Inhibiting PD-L1 Expression in Human Lung Cancer Cells

Author(s):

Fahad Khan, Pratibha Pandey*, Rashmi Mishra, Mohd. Arif, Ambuj Kumar, Asif Jafri and Rupa Mazumder   Pages 532 - 541 ( 10 )

Abstract:

<P>Aim: The aim of this study is to explore the therapeutic potential of S-allylcysteine (SAC) organosulphur compound as a potent immune checkpoint inhibitor PD-L1. </P><P> Background: Natural compounds have been showing tremendous anticancerous potential via suppressing the expression of genes involved in the development and progression of several carcinomas. This has further motivated us to explore the therapeutic potential of organosulphur compounds as potent immune checkpoint inhibitors. </P><P> Objective: Our study was designed to elucidate the potential of S-allylcysteine (SAC) as significant PD-L1 (immune checkpoint) inhibitor in human lung cancer A549 cancer cell line by using both the in vitro and in silico approaches. </P><P> Methods: Anticancerous effect of the SAC on lung cancer cells was determined by using the MTT cell viability. Apoptotic induction was confirmed by Hoechst staining, percent caspase-3 activity as well as gene expression analysis by real time PCR. Reactive Oxygen Species (ROS) was estimated by DCFDA method. Additionally, ligand-target protein interaction was analysed by molecular docking. </P><P> Result: Cell growth and proliferation was significantly reduced in SAC treated A549 cells in a concentration and time-dependent manner. The effect of SAC on apoptotic induction was analyzed by enhanced nuclear condensation, increased percent caspase-3 activity as well as modulation of apoptotic genes. Furthermore, SAC treatment also resulted in reduced expression of PD-L1 and HIF-1&#945;. Additionally, in silico analysis also supported the in vitro findings by showing efficient docking with PD-L1 immune checkpoint target. </P><P> Conclusion: Therefore, our results clearly suggested that SAC could serve as a novel chemotherapeutic candidate for the treatment of lung cancer by inhibiting immune checkpoint target PD-L1 in human lung cancer cells. Additionally, our study also explained a novel molecular mechanism of its antitumor activity.</P>

Keywords:

Lung cancer, immunotherapy, S-allylcysteine, apoptosis, PD-L1, ROS.

Affiliation:

Department of Biotechnology, Noida Institute of Engineering & Technology, 19, Knowledge Park-II, Institutional Area, Greater Noida, 201306, Department of Biotechnology, Noida Institute of Engineering & Technology, 19, Knowledge Park-II, Institutional Area, Greater Noida, 201306, Department of Biotechnology, Noida Institute of Engineering & Technology, 19, Knowledge Park-II, Institutional Area, Greater Noida, 201306, Department of Biotechnology, Noida Institute of Engineering & Technology, 19, Knowledge Park-II, Institutional Area, Greater Noida, 201306, Department of Biotechnology, Noida Institute of Engineering & Technology, 19, Knowledge Park-II, Institutional Area, Greater Noida, 201306, Molecular Endocrinology Laboratory, Department of Zoology, University of Lucknow, Lucknow, Noida Institute of Engineering & Technology (Pharmacy Institute), 19, Knowledge Park-II, Institutional Area, Greater Noida, 201306

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