Mechanistic Insights into 's Anti-proliferative and Pro-apoptotic Effects in A549 Lung Cancer Cells: Targeting PI3K/Akt Pathway and ROS Production

Overview

Journal Toxicol Res (Camb)

Publisher Oxford University Press

Date 2024 Sep 5

PMID 39233844

Authors

Mohammed Ali Alshehri

Mohamed Ali Seyed

Chellasamy Panneerselvam

Samy M Sayed

Mustafa Shukry

Affiliations

Soon will be listed here.

Abstract

Lung cancer, particularly non-small cell lung cancer (NSCLC), is a leading cause of cancer-related deaths worldwide. This study investigates the molecular mechanisms behind the anti-cancer effects of the tropical desert plant on the A549 NSCLC cell line. The research examined anti-proliferative effects, cytotoxicity, apoptosis, reactive oxygen species (ROS) generation, mitochondrial membrane potential, and cell morphology in NSCLC A549 and L-132 cells. In addition, the influence of on DNA fragmentation, apoptotic signaling, and PI3K/Akt pathways for its anti-cancer mechanism was examined. Our results indicated that effects were dose- and time-dependent to exhibit anti-proliferative effects on A549 cells. treatment promoted apoptotic cell death cycle arrest, increased apoptotic cells, depolarized the mitochondrial membrane, and induced morphological alterations in cells and nuclei. It also inhibited A549 cell migration ( < 0.05), colonization, and invasiveness. Moreover, the study demonstrated that treatment resulted in the upregulation of Bax expression, downregulation of Bcl-2 expression, and apoptotic fragmented DNA in A549 cells. The top five bioactive compounds derived from exhibited molecular interactions that inhibit PIK3CA and AKT1. This inhibition leads to an increased frequency of apoptosis and subsequent death of cancer cells. Additionally, extract induced an increase in ROS formation and cytochrome c levels, indicating that its toxic effects on A549 cells involve both ROS-dependent cytotoxicity through the disruption of mitochondrial transmembrane potential ΔΨm and ROS-independent cell cycle arrest through downregulation BCL-2, PARP, E-Cadherin, PI3K, and Akt expressions pathways.

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